Abeta-peptide length and apolipoprotein E genotype in Alzheimer's disease.
Apolipoprotein E (ApoE) epsilon4 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 (Abeta) peptides of different length (Abeta1-40 and Abeta1-42) and found that the increased plaque frequency observed with epsilon4 genotypes may be largely attributed to an increase in Abeta1-40-positive plaques. Indeed, both the number of Abeta1-40-positive plaques, as well as the ratio of Abeta1-40/Abeta1-42-positive plaques, increased with epsilon4 dosage. In contrast, the frequency of Abeta1-42-immunoreactive plaques was similar for epsilon3/epsilon3, epsilon3/epsilon4, and epsilon4/epsilon4 genotypes. ApoE may influence Abeta1 length by facilitating Abeta1-40 deposition onto Abeta1-42-seeded plaques or by modulating the activity of a putative carboxypeptidase that forms Abeta1-40 from Abeta1-42 in situ.
Gearing
M
M
VA Medical Center, Decatur, Georgia 30033, USA.
Mori
H
H
Mirra
S S
SS
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000648:ultrastructure*; D001057:Apolipoproteins E / Q000235:genetics*; D002268:Carboxypeptidases / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000503:physiopathology / Q000648:ultrastructure; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D002268:Carboxypeptidases