Increased amyloid β-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease

Amyloid β-peptide (Aβ) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in Aβ deposition in late-onset AD might be related to apolipoprotein E genotype (APOE gene; the two most common alleles are 3 and 4), since APOE4 is a susceptibility gene for late-onset AD and apolipoprotein E interacts strongly with Aβ in vitro. In an autopsy series of brains of late-onset AD patients, we found a strong association of APOE4 allele with increased vascular and plaque Aβ deposits. Late-onset AD patients with one or two APOE4 alleles have a distinct neuropathological phenotype compared with patients homozygous for APOE3.