title: APOE-ε2 and APOE-ε4 correlate with increased amyloid accumulation in cerebral vasculature.
abstract: The APOE-ε4 allele correlates with increased risk of Alzheimer disease (AD) and increased parenchymal amyloid plaques. We tested how the APOE genotype correlated with cerebral amyloid angiopathy (CAA) by analyzing 371 brains for parenchymal and meningeal CAA in 4 brain regions (frontal, parietal, temporal, and occipital neocortex). The overall severity of CAA was highest in the occipital lobe. APOE-ε4/4 brains (n = 22) had the highest levels of CAA across regions. In the occipital lobe, nearly all APOE-ε4/4 cases were scored with the highest level of CAA (meninges, 95% of cases; parenchyma, 81%). In this brain region as in others, APOE-ε3/4 brains (n = 115) showed consistently less CAA than APOE-ε4/4 brains (meninges, 43%; parenchyma, 43%). APOE-ε3/3 brains (n = 182) showed even less CAA (meninges, 19%; parenchyma, 19%). Interestingly, APOE-ε2/3 cases (n = 42) had more CAA than APOE-ε3/3 (meninges, 44%; parenchyma, 32%), despite a reduced risk for AD in the APOE-ε2/3 individuals. APOE-ε4/4 brains also had the fewest regions without CAA, whereas APOE-ε3/3 brains had the most. Ordinal regression analyses demonstrated significant impacts of APOE-ε2 and APOE-ε4 on CAA at least in some brain regions. These data demonstrate that APOE genotype correlations with Aβ deposition in CAA only incompletely correspond to other AD-linked brain pathologies.
authors.affiliation: Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.forename: Nina M
authors.initials: NM
authors.lastname: Pious
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.forename: Donna M
authors.initials: DM
authors.lastname: Wilcock
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.forename: Steven
authors.initials: S
authors.lastname: Estus
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053329:Apolipoprotein E2 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001808:Blood Vessels / Q000378:metabolism*; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male
chemical_list: D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4