Human herpes viruses are associated with steeper age-dependent increases of serum biomarkers for dementia in cognitively unimpaired women
Blood biomarkers for dementia are being increasingly used for screening and possibly early detection of dementia in cognitively unimpaired (CU) people. Here we measured blood serum levels of 5 dementia-related biomarkers (A^I^21^aEUR"40 [A^I^240], A^I^21^aEUR"42 [A^I^242], A^I^242/A^I^240 ratio, phosphorylated Tau181 [pTau181], and phosphorylated Tau217 [pTau217]) and determined the seroprevalence of 6 HHV (HHV1, HHV2, HHV3, HHV4, HHV5, HHV6) in 345 samples drawn at successive visits from 167 CU women 26^aEUR"98 years old. All biomarkers except for A^I^242/A^I^240 increased significantly with age, particularly in those who were HHV seropositive. With respect to the biomarkers, the increase was highest for A^I^240^aEURo/oo>^aEURo/ooA^I^242^aEURo/oo>^aEURo/oopTau217^aEURo/oo>^aEURo/oopTau181, and, with respect to HHV, the increase was highest for HHV4^aEURo/oo>^aEURo/ooHHV6^aEURo/oo>^aEURo/ooHHV1^aEURo/oo>^aEURo/ooHHV2^aEURo/oo>^aEURo/ooHHV5 (HHV3 was seropositive in all samples). Overall, the average normalized rate of increase of biomarkers with age was 2.15^aEURo/oo~A-^aEURo/oohigher in the HHV seropositive vs. seronegative groups (P^aEURo/oo=^aEURo/oo0.003, paired samples t-test). The presence of Apolipoprotein EApolipoprotein 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 (ApoEApolipoprotein 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) genotype did not have a significant effect on those rates. These findings document a link between prior viral infection and dementia-related blood biomarkers, adding support to the HHV hypothesis in developing dementia, irrespective of ApoEApolipoprotein 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 presence.