APOE, vascular pathology, and the AD brain.
OBJECTIVE
To use neuropathologic data to examine the association between APOE genotype and cerebrovascular lesions commonly found in Alzheimer disease (AD), as well as neuritic senile plaque (SP) and neurofibrillary tangle (NFT) burden.


METHODS
The sample comprised brains from 96 men and 3 women who fulfilled NIA-Reagan criteria for intermediate to high likelihood of AD. Region-specific and global measures of gross cerebrovascular disease, arteriolosclerosis, white matter lesions, microinfarcts, amyloid angiopathy, neuritic SP, and NFT burden were compared among those who had at least one APOE-epsilon4 vs those who did not. Pairwise rank-order correlations between measures were calculated. The association between APOE epsilon4 status and measures of vascular and AD pathology, adjusting for age at death, sex, brain weight, and Braak stage, were evaluated.


RESULTS
APOE-epsilon4 was not associated with gross cerebrovascular pathology. Compared to those who were negative, brains from epsilon4 individuals had a greater degree of small vessel arteriolosclerosis (p = 0.04) and perivascular macrophage infiltration (p = 0.06), but not other markers of small vessel disease or white matter myelin loss. Microinfarcts in the deep nuclei were associated with epsilon4 (p = 0.009), whereas cortical and subcortical microinfarcts were not. There was a trend toward association between APOE genotype and amyloid angiopathy (p = 0.08), and epsilon4 was associated with neuritic SP burden, but not NFT.


CONCLUSIONS
APOE-epsilon4 is associated with small vessel arteriolosclerosis, microinfarcts of the deep nuclei, neuritic senile plaque density, and amyloid angiopathy in patients with autopsy-proven Alzheimer disease (AD). These results suggest a role for epsilon4 in some of the microvascular changes commonly found in AD and are consistent with a potential amyloidogenic role for epsilon4.
Yip
A G
AG
Department of Medicine, Boston University School of Medicine, Bedford, MA, USA.
McKee
A C
AC
Green
R C
RC
Wells
J
J
Young
H
H
Cupples
L A
LA
Farrer
L A
LA
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D020520:Brain Infarction / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002536:Cerebral Arteries / Q000473:pathology* / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E