Objective: To test the association of distinct neuropathologic features of Alzheimer disease (AD) with risk loci identified in genome-wide association studies.
Methods: Vantaa 85+ is a population-based study that includes 601 participants aged ≥85 years, of which 256 were neuropathologically examined. We analyzed 29 AD risk loci in addition to ε4, which was studied separately and used as a covariate. Genotyping was performed using a single nucleotide polymorphism (SNP) array (341 variants) and imputation (6,038 variants). Participants with Consortium to Establish a Registry for Alzheimer Disease (CERAD) (neuritic Aβ plaques) scores 0 (n = 65) vs score M + F (n = 171) and Braak (neurofibrillary tangle pathology) stages 0-II (n = 74) vs stages IV-VI (n = 119), and with capillary Aβ (CapAβ, n = 77) vs without (n = 179) were compared. Cerebral amyloid angiopathy (CAA) percentage was analyzed as a continuous variable.
Results: Altogether, 24 of the 29 loci were associated (at < 0.05) with one or more AD-related neuropathologic features in either SNP array or imputation data. Fifteen loci associated with CERAD score, smallest = 0.0002122, odds ratio (OR) 2.67 (1.58-4.49) at locus. Fifteen loci associated with Braak stage, smallest = 0.004372, OR 0.31 (0.14-0.69) at locus. Twenty loci associated with CAA, smallest = 7.17E-07, β 14.4 (8.88-20) at locus. Fifteen loci associated with CapAβ smallest = 0.002594, OR 0.54 (0.37-0.81) at locus. Certain loci associated with specific neuropathologic features. , , and associated only with CAA, while and associated only with CapAβ.
Conclusions: AD risk loci differ in their association with neuropathologic features, and we show for the first time distinct risk loci for CAA and CapAβ.
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| http://dx.doi.org/10.1212/NXG.0000000000000211 | DOI Listing |
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