Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.
Amyloid beta-peptide (A beta) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in A beta 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 A beta 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 A beta deposits. Late-onset AD patients with one or two APOE4 alleles have a distinct neuropathological phenotype compared with patients homozygous for APOE3.
Schmechel
D E
DE
Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710.
Saunders
A M
AM
Strittmatter
W J
WJ
Crain
B J
BJ
Hulette
C M
CM
Joo
S H
SH
Pericak-Vance
M A
MA
Goldgaber
D
D
Roses
A D
AD
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics*; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism*; D004198:Disease Susceptibility; D006720:Homozygote; D006801:Humans; D016874:Neurofibrillary Tangles / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D011446:Prospective Studies; D012189:Retrospective Studies
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D016900:Neurofilament Proteins