Aβ‐peptide length aid apolipoprotein E genotype in Alzheimer's disease

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Abstract
Apolipoprotein ∈ (ApoE)ε4 allele, a risk factor for the development of Alzheimer's disease (AD), is associated with increased amyloid deposition. We examined cerebral cortex in 68 AD cases using antibodies to βbeta;-amyloid (Aβbeta;) peptides of different length (Aβbeta;1−40 and Aβbeta;l−42) and found that the increased plaque frequency observed with ε4 genotypes may be largely attributed to an increase in Aβbeta;1−40-positive plaques. Indeed, both the number of Aβbeta;1−40-positive plaques, as well as the ratio of Aβbeta;I−40/ Aβbeta;1−42-positive plaques, increased with ε4 dosage. In contrast, the frequency of Aβbeta;1−42-immunoreactive plaques was similar for ε3/ε3,ε3/ε4 and ε4/ε4 genotypes. ApoE may influence Aβbeta; length by facilitating Aβbeta; 1−40 deposition onto Aβbeta;1−42-seeded plaques or by modulating the activity of a putative carboxypeptidase that forms Aβbeta;1−40 from Aβbeta;1−42 in situ.