APOE-ε2 and APOE-ε4 Correlate With Increased Amyloid Accumulation in Cerebral Vasculature

The APOE-epsilon 4 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? 4/4 brains (n = 22) had the highest levels of CAA across regions. In the occipital lobe, nearly all APOE-epsilon 4/4 cases were scored with the highest level of CAA (meninges, 95% of cases; parenchyma, 81%). In this brain region as in others, APOE-epsilon 3/4 brains (n = 115) showed consistently less CAA than APOE-epsilon 4/4 brains (meninges, 43%; parenchyma, 43%). APOE-epsilon 3/3 brains (n = 182) showed even less CAA (meninges, 19%; parenchyma, 19%). Interestingly, APOE-epsilon 2/3 cases (n = 42) had more CAA than APOE-epsilon 3/3 (meninges, 44%; parenchyma, 32%), despite a reduced risk for AD in the APOE-epsilon 2/3 individuals. APOE-epsilon 4/4 brains also had the fewest regions without CAA, whereas APOE-epsilon 3/3 brains had the most. Ordinal regression analyses demonstrated significant impacts of APOE-epsilon 2 and APOE-epsilon 4 on CAA at least in some brain regions. These data demonstrate that APOE genotype correlations with AA deposition in CAA only incompletely correspond to other AD-linked brain pathologies.