Women's Healthy Brain News

Celebrating 10 Years

2021-11-05
10 years of research regarding Women's Healthy and Brain Resilience. Click below to find out more about the research we have performed.

Woman Strong

Justin Harris (University of Minnesota Legacy) - 2020-05-01
It was 2010, and Kunin and her friends and fellow philanthropists Barbara Forster and Sally Kling were meeting with Apostolos Georgopoulos, a Regents Professor and McKnight Presidential Chair in Cognitive Neuroscience at the University of Minnesota Medical School. Georgopoulos was asking for their support in launching a first-of-its-kind study of women's brain health across the lifespan.

He wanted to know: Why do some women show signs of cognitive decline as they age while others do not?

Kunin, Forster, and Kling were interested in helping him find answers. They shared the idea with other like-minded women, hosting small fundraising gatherings and meet-and-greets with Georgopoulos, and sent letters to more than 170 people asking for gifts of any size...

Dementia Prevention Linked to Disposal of Pathogenic Debris

UMN Inquiry - Deane Morrison - 2020-02-21


What if surviving an infection like herpes, pneumonia, or Lyme desease set you up for dementia later in life?

For some people that is, sadly, the case, studies by two University of Minnesota researchers indicate. Evidence is mounting that proteins in fragments of bacteria, viruses, or other pathogens left over from battles with our immune system can harm the brain and raise the chance of dementia. These proteins are all termed "antigenic" - i.e., able to provoke an immune response, especially one involving antibody production.

But Lisa James, PhD, and Apostolos Georgopoulos, MD, PhD, have also found that many people have genes that shield against such an outcome. And now they have demonstrated their beneficial effects across the populations of entire countries.



Article Continued at Publisher's Site.

Dementias Caused by Persistent Pathogens and the Protective Role of
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Against them

Journal of Neurology & Neuromedicine - 2019-12-27James L, Georgopoulos AP
Dementia is a leading cause of death worldwide, representing a significant global burden. In addition to genetic and lifestyle factors that have been widely linked to dementia, pathogens are increasingly recognized as contributing to the development of dementia. Here we discuss the role of human leukocyte antigens (
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
) in maintaining brain health by facilitating the elimination of pathogens and highlight evidence suggesting that the inability to eliminate pathogens contributes to dementia. Finally, we briefly review common forms of dementia including Alzheimer's disease, vascular dementia, frontotemporal dementia, Lewy body dementia, and prion dementia in an effort to contextualize the role of persistent pathogens across the various dementia phenotypes.

The
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1*13:02 Allele Protects against Dementia in Continental Western Europe

Journal of Neurology & Neuromedicine - 2019-09-09James L, Georgopoulos AP
HLA Class II DRB1*13 alleles have recently been found to protect against age-related brain deterioration, even in the presence of
Apolipoprotein E

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 (
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4), suggesting a possible protection against dementia. Here we evaluated the association between the population frequency of common DRB1*13 alleles and the prevalence of dementia in Continental Western Europe. Prevalence of dementia in Continental Western Europe was derived from published reports on dementia frequency from the Global Burden of Disease Study 2016 and population totals obtained from the Population Reference Bureau. DRB1*13:01 and DRB1*13:02 allele frequencies were obtained from a publicly available database (allelefrequency.net) and
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
was obtained from published reports on the world distribution of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4. The prevalence of dementia in 14 Continental Western European (CWE) countries, where life expectancy is practically identical, significantly decreases exponentially with increasing frequency of DRB1*13:02 (R2 = 0.452, P = 0.008), even when adjusted for the prevalence of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 allele, a known risk factor for Alzheimer's disease. This finding documents the protective effect of DRB1*13:02 on dementia prevalence in CWE. Since the function of
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
class II genes is to aid in the elimination of pathogens by enabling the production of antibodies against their antigens in specific immunity, the protective effect of DRB1*13:02 points to the presence of persistent harmful antigens as causal factors in development of dementia, antigens specific to DRB1*13:02 that could not be eliminated in its absence.

Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
as a Key Factor in Preventing Dementia and Associated
Apolipoprotein E

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 Risk

Frontiers in Aging Neuroscience - 2019-04-12James L, Georgopoulos AP10.3389/fnagi.2019.00082
Itzhaki's (2018) recent review discusses the evidence for a role of herpes virus (mainly herpes virus 1) in the development of Alzheimer's disease (AD), particularly among genetically vulnerable individuals. Specifically, the viral concept proposes that latent herpes virus in the brain of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 (
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4) carriers is intermittently reactivated causing cumulative damage that ultimately results in AD. The viral concept and collective findings are particularly intriguing given the potential for intervention for AD aimed at neutralizing or eliminating herpes virus. Here we discuss
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
as an additional genetic link in the viral concept of AD that not only accounts for the role of herpes virus in AD, but also extends to other viruses that may contribute to AD and to other diseases, and is consistent with beneficial brain effects of treatments aimed at eliminating the damaging effects of herpes virus via antivirals or IVIG as discussed in the review.

The effects of
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1*13 and
Apolipoprotein E

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
on age-related variability of
Synchronous Neural Interactions

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
in healthy women

Background

Age-related brain changes are well-documented and influenced by genetics. Extensive research links
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
to brain function, with the E4 allele serving as a risk factor for brain disease, including Alzheimer's disease, and the E2 allele conferring protection. Recent evidence also supports protective effects of another gene,
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1*13, on brain disease and age-related brain atrophy in cognitively healthy adults. Here we investigated the effects of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
and
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1*13 on brain function by examining changes in neural network properties with age in healthy adults.

Methods

One hundred seventy-eight cognitively healthy women (28-99 y old) underwent a magnetoencephalography scan and provided a blood sample for genetic analysis. Age-related changes in neural network variability in genetic subgroups of DRB1*13 X
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
genotype combinations were assessed using linear regression of network variability against age.

Findings

For individuals lacking a DRB1*13 allele and/or carrying an
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4 allele, network variability increased significantly with age. In contrast, no such increase was observed in the presence of DRB1*13 and/or
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
2.

Interpretation

These findings extend previous research documenting the protective effect of DRB1*13 on brain structure to include protection against age-related changes in brain function, and demonstrate similar protective effects on neural network variability for either DRB1*13 or
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
2. These protective effects could be due to reduction or elimination of factors known to disrupt brain function, including neuroinflammation and amyloid beta protein.

Funding

U.S. Department of Veterans Affairs, and University of Minnesota.

Minnesota Women's Healthy Brain Aging Project: Past, Present, and Future

2018-06-12
Lisa James, PhD, holder of the , presented her work at the University of Minnesota on June 12th, 2018. She, along with the project coordinator, Stacy Dolan, RN are shown describing and seeking support from an appreciative audience. Two attendees are shown with project assistant Rachel Johnson (right).

To learn more about our work and how you can support it, visit

Protective Effect of
Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
Allele DRB1*13:02 on Age-Related Brain Gray Matter Volume Reduction in Healthy Women

Background

Reduction of brain volume (brain atrophy) during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the
HLA

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
allele DRB1*13:02 which prevents brain atrophy in
Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.
(James et al., 2017).

Methods

Seventy-one cognitively healthy women (32-69 years old) underwent a
Structural Magnetic Resonance Imaging

Structural Magnetic Resonance Imaging (sMRI)

Performed to assess gray-matter volume. The data are acquired using a Philips 3T Achieva XL magnet with a SENSE 8 channel head coil. Approximately 500,000 voxels per brain are analyzed. In the first analysis, the volume of about 100 separate brain regions is calculated using FreeSurfer software (www.surfer.nmr.mgh.harvard. edu). This provides a coarse-grain, volumetric analysis of areas of the brain. In the second analysis, called voxel-based morphometry, the density of each voxel is assessed for a fine-grain analysis of each area.5 Typically, gray-matter volume decreases with age but at rates that are different for different people, for different areas of the brain, and for men and women. In that sense, one can talk about "gray-matter age" versus chronological age. A person may be 68 years old but have the gray-matter volume of a 50-year-old. Defining brain age based on measurements (as contrasted with chronological age) is a pervasive theme in this project.
scan to measure the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter. Participants were assigned to two groups, depending on whether they lacked the DRB1*13:02 allele (No DRB1*13:02 group, N = 60) or carried the DRB1*13:02 allele (N = 11). We assessed the change of brain gray matter volume with age in each group by performing a linear regression where the brain volume (adjusted for total intracranial volume) was the dependent variable and age was the independent variable.

Findings

In the No DRB1*13:02 group, the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter were reduced highly significantly. In contrast, none of these volumes showed a statistically significant reduction with age in the DRB1*13:02 group.

Interpretation

These findings document the protective effect of DRB1*13:02 on age-dependent reduction of brain gray matter in healthy individuals. Since the role of this allele is to connect to matching epitopes of external antigens for the subsequent production of antibodies and elimination of the offending antigen, we hypothesize that its protective effect may be due to the successful elimination of such antigens to which we are exposed during the lifespan, antigens that otherwise would persist causing gradual brain atrophy. In addition, we consider a possible beneficial role of DRB1*13:02 attributed to its binding to cathepsin S, a known harmful substance in brain aging (Wendt et al., 2008). Of course, other factors covarying with the presence of DRB1*13:02 could be involved.

The Exploration of Dietary Habits Associated with Healthy Brain Functioning Across the Lifespan

Society for Neuroscience - 2016-01-01Mathison JH, James L, Hoover H, Georgopoulos A, Georgopoulos AP
The Healthy Brain Project (HBP) is a unique study at the
Brain Sciences Center

Brain Sciences Center (BSC)

A research group in collaboration with the Minnesota American Legion, Minneapolis VA Medical Center, and the University of Minnesota.
that integrates neuroimaging, genetics, cognitive, and lifestyle data in order to identify characteristics associated with healthy brain aging [1]. Participants are cognitively healthy women veterans from ealty adulthood to advanced old age. Collecting such data from a healthy population could allow for more detailed identification of dietary habits associated with healthy brain function across the lifespan.

Neural Network Decorrelation for Healthy Brain Aging: A Cross-sectional and Longitudinal
Magnetoencephalography

Magnetoencephalography (MEG)

A noninvasive technique that detects magnetic fields above the surface of the head produced by postsynaptic potentials in the brain.
study

Society for Neuroscience - 2016-01-01James L, Leuthold A, Georgopoulos A, Chorn C, Mathison JH, Georgopoulos AP
Neural network decorrelation is fundamental to information processing. Specifically, ensemble freedom is constrained by correlations amount network elements: a network with least correlated elements provides maximum independence (i.e., zero mutual information) and hence entails maximum possibilities for encoding information.

We have previously demonstrated that neural decorrelation, primarily involving temporal regions, distinguishes healthy veterans from those with psychiatric disorders, and have hypothesized that network decorrelation underlies healthy brain functioning by permitting neural flexibility (James et al., JAMA Psychiatry 70:410-418). In the present study (http://healthybrain.umn.edu/), we tested the hypothesis that in cognitively healthy individuals, decorrelation would increase with age, serving as a mechanism that promotes efficient information processing and neural flexibility to maintain healthy brain functioning across the lifespan.

The number of cysteine residues per mole in
Apolipoprotein E

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
affects systematically
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
in women's healthy brains

Experimental Brain Research - 2013-05-01Leuthold A, Mahan M, Stanwyck JJ, Georgopoulos A, Georgopoulos AP10.1007/s00221-013-3464-x
ApoE is involved in lipid metabolism in the brain, but its effects on brain function are not understood. Three
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
isoforms (E4, E3, and E2) are the result of cysteine-arginine interchanges at two sites: there are zero interchanges in E4, one interchange in E3, and two interchanges in E2. The resulting six
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
genotypes (E4/4, E4/3, E4/2, E3/3, E3/2, E2/2) yield five groups with respect to the number of cysteine residues per mole (CysR/mole), as follows.
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
4/4 has zero cysteine residues per mole (0-CysR/mole), E4/3 has one (1-CysR/mole), E4/2 and E3/3 each has two (2-CysR/mole), E3/2 has three (3-CysR/mole), and E2/2 has four (4-CysR/mole). The use of the number of CysR/mole to characterize the
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
molecule converts the categorical
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
genotype scale, consisting of 6 distinct genotypes above, to a 5-point continuous scale (0-4 CysR/mole). This allows the use of statistical analyses suitable for continuous variables (e.g. regression) to quantify the relations between various variables and
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
. Using such analyses, here, we show for the first time that
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
affects in a graded and orderly manner neural communication, as assessed by analyzing the relation between the number of CysR/mole and
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
measured by
Magnetoencephalography

Magnetoencephalography (MEG)

A noninvasive technique that detects magnetic fields above the surface of the head produced by postsynaptic potentials in the brain.
in 130 cognitively healthy women. At the one end of the CysR/mole range, the 4-CysR/mole (E2/2)
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
distribution had the highest mean, lowest variance, lowest range, and lowest coefficient of variation, whereas at the other end, 0-CysR/mole (E4/4)
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
distribution had the lowest mean, highest variance, highest range, and highest coefficient of variation. The special status of the 4-CysR/mole distribution was reinforced by the results of a hierarchical tree analysis where the 4-CysR/mole (E2/2)
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
distribution occupied a separate branch by itself and the remaining CysR/mole
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
distributions were placed at increasing distances from the 4-CysR/mole distribution, according to their number of CysR/mole, with the 0-CysR/mole (E4/4) being farthest away. These findings suggest that the 4-CysR/mole (E2/2)
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
distribution could serve as a reference distribution. When the
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
distributions of individual women were expressed as distances from this reference distribution, there was a substantial overlap among women of various CysR/mole. This refocuses the placement of individual brains along a continuous distance from the 4-CysR/mole
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
distribution, in contrast to the common categorical assignment to a specific
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
genotype. Finally, the orderly variation of
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
with the number of CysR/mole found here is in keeping with recent advances and ideas regarding the molecular mechanisms underlying the differential effects of
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
in the brain which emphasize the healthier stability conferred on the
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
molecule by the increasing number of cysteine-arginine interchanges, with 4-CysR/mole (E2/2) being the best case, as opposed to the instability and increased chance of toxic fragmentation of the
ApoE

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.
molecule with lower number of CysR/mole, with 0-CysR/mole (E4/4) as the worst case (Mahley and Huang in Neuron 76:871-885, 2012a). However, our results also document the appreciable variation of
SNI

Synchronous Neural Interactions (SNI)

Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG.
properties within the various CysR/mole groups and individuals which points to the existence and important role of other factors involved in shaping brain function at the network level.

The Minnesota Women Healthy Aging Project

Minnesota Medicine - 2012-01-01Georgopoulos AP
The brain is the most complex organ in the body. It consists of more than 100 billion cells. (Compare that with the human population, which is only 7 billion.) Unlike the cells of any other organ, brain cells interact extensively with each other every millisecond. The brain's nature as a dynamic, massively interconnected network is the basis for its ability to process information. It is also the basis for learning, memory, and plasticity. These latter properties are formalized as changes in brain function, and they take place throughout our lives. These changes are cumulative, as illustrated by how our education, memories, habits, and injuries build on each other, whether we like it or not. Our understanding of the brain's cumulative nature forms the basis for all sorts of interventions, giving us hope that they will have a lasting effect.