APOE-ε2 and APOE ε4 correlate with increased amyloid accumulation in cerebral vasculature

The APOE-ε4 allele correlates with i ncreased 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-[Latin Small Letter Open E]3/4 brains (n = 115) showed consistently less CAA than APOE-ε4/4 brains (meninges, 43%; parenchyma, 43%). APOE-[Latin Small Letter Open E]3/3 brains (n = 182) showed even less CAA (meninges, 19%; parenchyma, 19%). Interestingly, APOE-[Latin Small Letter Open E]2/3 cases (n = 42) had more CAA than APOE-[Latin Small Letter Open E]3/3 (meninges, 44%; parenchyma, 32%), despite a reduced risk for AD in the APOE-[Latin Small Letter Open E]2/3 individuals. APOE-ε4/4 brains also had the fewest regions without CAA, whereas APOE-[Latin Small Letter Open E]3/3 brains had the most. Ordinal regression analyses demonstrated significant impacts of APOE-[Latin Small Letter Open E]2 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.