The ability 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.
fragments to promote intraneuronal accumulation of amyloid beta peptide 42 is both isoform and size-specific

Scientific Reports - 2016-08-01Dafnis I, Argyn L, Sagnou M, Tzinia A, Tsilibary EC, Stratikos E, Chroni A10.1038/srep30654
The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer's disease (AD).
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 is more susceptible to proteolysis than
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 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.
3 isoforms and carboxyl-terminal truncated
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 forms have been found in AD patients' brain. We have previously shown that 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.
4 fragment,
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.
4-165, promotes amyloid-peptide beta 42 (Aβ42) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis. Here, we show that these effects are allele-dependent and absolutely require 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.
4 background. Furthermore, the exact length of the fragment is critical since longer or shorter length carboxyl-terminal truncated
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 forms do not elicit the same effects. Structural and thermodynamic analyses showed 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.
4-165 has a compact structure, in contrast to other carboxyl-terminal truncated
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 forms that are instead destabilized. Compared however to other allelic backgrounds,
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.
4-165 is structurally distinct and less thermodynamically stable suggesting that the combination of a well-folded structure with structural plasticity is a unique characteristic of this fragment. Overall, our findings suggest that the ability 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.
fragments to promote Aβ42 intraneuronal accumulation is specific for both 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.
4 isoform and the particular structural and thermodynamic properties of the fragment.