A beta-peptide length and apolipoprotein E genotype in Alzheimer's disease

Apolipoprotein E (ApoE) epsilon 4 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 beta-amyloid (A beta) peptides of different length (A beta(1-40) and A beta(1-42)) and found that the increased plaque frequency observed with epsilon 4 genotypes may be largely attributed to an increase in A beta(1-40)-positive plaques. Indeed, both the number of A beta(1-40)-positive plaques, as web as the ratio Of A beta(1-40)/A beta(1-42)-positive plaques, increased with epsilon 4 dosage. In contrast, the frequency of A beta(1-42)-immunoreactive plaques was similar for epsilon 3/epsilon 3, epsilon 3/epsilon 4, and epsilon 4/epsilon 4 genotypes. ApoE may influence A beta length by facilitating A beta(1-40) deposition onto A beta(1-42)-seeded plaques or by modulating the activity of a putative carboxypeptidase that forms A beta(1-40) from A beta(1-42) in situ.