APOE and cerebral amyloid angiopathy in community-dwelling older persons

Both cerebral amyloid angiopathy and Alzheimer's disease pathology involve abnormal beta-amyloid processing. We aim to elucidate the relationship of the apolipoprotein E (APOE) genotypes with amyloid angiopathy in the presence of variable amounts of Alzheimer's pathology. Data came from 1062 autopsied subjects from 2 community-based studies of aging. Common neuropathologies including Alzheimer's disease and amyloid angiopathy were assessed using uniform methods. APOE was genotyped by sequencing the 2 polymorphisms in codons 112 and 158 of exon 4. We examined the associations of APOE with amyloid angiopathy using ordinal logistic regression analyses, controlling for demographics and subsequently Alzheimer's and other common pathologies. Moderate to severe amyloid angiopathy was identified in 35.2% (n = 374) of the subjects; 15.3% (n = 162) of the subjects were APOE epsilon 2 carriers; and 26.1% (n = 277) epsilon 4 carriers. Adjusting for demographics, the presence of epsilon 4 allele, but not epsilon 2, was associated with more severe amyloid angiopathy. After further adjustment for Alzheimer's pathology, both epsilon 2 (odds ratio 1.707, 95% confidence interval 1.236-2.358, p = 0.001) and epsilon 4 (odds ratio 2.284, 95% confidence interval 1.730-3.014, p < 0.001) were independently associated with amyloid angiopathy. The results were confirmed by path analysis. Furthermore, APOE epsilon 4 carriers, but not epsilon 2 carriers, were more likely to have capillary amyloid angiopathy. Accounting for capillary involvement did not alter the APOE associations with amyloid angiopathy. We conclude that both APOE epsilon 2 and epsilon 4 alleles are associated with more severe cerebral amyloid angiopathy, and the direct effect of epsilon 2 is masked by the allele's negative association with comorbid Alzheimer's pathology. APOE epsilon 4, but not epsilon 2, is associated with capillary amyloid angiopathy. (C) 2015 Elsevier Inc. All rights reserved.