Capillary Amyloid-beta Protein Deposition in a Population-Based Study (Vantaa 85+)

Background: Capillary amyloid-beta (capA beta) deposition in the cerebral cortex is the neuropathological feature providing the basis for categorizing cerebral amyloid angiopathy (CAA) into two distinct types, CAA-Type1 with capA beta and CAA-Type2 without capA beta. Objective: We investigated the neuropathological and clinical characteristics of capA beta deposition in a prospective population-based study. Methods: Vantaa 85+ includes 601 individuals aged >= 85 years, of which 300 were studied clinically and neuropathologically. 278 subjects were analyzed for the apolipoprotein E (APOE) genotype. The diagnosis of capA beta was determined using immunohistochemistry against A beta, and of CAA using Congo red confirmed by A beta immunohistochemistry, both analyzed in six brain areas. The severity of capA beta was graded semi-quantitatively, and the severity of CAA was based on the percentage of affected vessels. Alzheimer's disease (AD)-type neuropathology (CERAD score and Braak stage) was analyzed using standard methods. Results: CAA-Type1 was present in 86/300, CAA-Type2 in 135/300, and 79/300 had no CAA. CapA beta was most frequent in the occipital lobe (79/86). CAA-Type1 was associated with the severity of CAA (p < 0.001), dementia (p < 0.001), severe AD-type neuropathology (p-value 0.09 for CERAD C and 0.017 for Braak stages V-VI), and APOE epsilon 4 allele carrier status (p < 0.001). Conclusions: This population-based study confirmed the presence of distinct CAA-Type1 and its association with the severity of CAA, severe AD-type neuropathology, and the APOE epsilon 4 carrier status. Both the severity and localization of the deposition seemed to determine the clinical significance of capA beta.