Regional distribution of mineralized blood vessels in Alzheimer disease and clinicopathological associations: A multicenter autopsy study.

Abstract

Mineralized blood vessels (MBV) are a form of vascular pathology associated with cerebrovascular aging and neurodegeneration; however, their regional distribution and clinicopathological correlates in Alzheimer disease (AD) remain poorly characterized. We examined 265 decedents with intermediate/high AD neuropathologic change from three Alzheimer's Disease Research Centers (Columbia University, University of California San Diego, and University of California Davis). Hematoxylin and eosin-stained sections from the posterior hippocampus, putamen, and globus pallidus were evaluated for MBV. Associations with demographic, clinical, genetic, and neuropathological variables were assessed using bivariate tests and multivariable logistic regression adjusting for age at death, sex, ethnicity, and center. MBV frequency differed across regions, with highest involvement in the globus pallidus (58.3%), followed by the posterior hippocampus (28.6%), and putamen (13.8%) (all pairwise p < 0.001). After covariate adjustment, MBV presence was not associated with sex, ethnicity, education, APOE ε4 carrier status, or cerebral amyloid angiopathy (CAA). After correction for multiple comparisons, MBV remained associated with état criblé in the putamen and globus pallidus (both FDR-adjusted p < 0.01), and concomitant Lewy body disease remained associated with reduced MBV presence in the posterior hippocampus and globus pallidus (both FDR-adjusted p < 0.05). Nominal associations with a history of transient ischemic attack (TIA) did not remain significant after correction for multiple comparisons. This study identified MBV as a regionally selective feature of cerebrovascular aging in AD, enriched in deep gray matter. MBV may contribute to regional vulnerability and pathological heterogeneity in the aging AD brain.