Acta Neuropathologica Communications (Jun 2023)

The neuropathological landscape of Hispanic and non-Hispanic White decedents with Alzheimer disease

  • Rebeca Scalco,
  • Naomi Saito,
  • Laurel Beckett,
  • My-Le Nguyen,
  • Emily Huie,
  • Hsin-Pei Wang,
  • Delaney A. Flaherty,
  • Lawrence S. Honig,
  • Charles DeCarli,
  • Robert A. Rissman,
  • Andrew F. Teich,
  • Lee-Way Jin,
  • Brittany N. Dugger

DOI
https://doi.org/10.1186/s40478-023-01574-1
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 14

Abstract

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Abstract Despite the increasing demographic diversity of the United States’ aging population, there remain significant gaps in post-mortem research investigating the ethnoracial heterogeneity in the neuropathological landscape of Alzheimer Disease (AD). Most autopsy-based studies have focused on cohorts of non-Hispanic White decedents (NHWD), with few studies including Hispanic decedents (HD). We aimed to characterize the neuropathologic landscape of AD in NHWD (n = 185) and HD (n = 92) evaluated in research programs across three institutions: University of California San Diego, University of California Davis, and Columbia University. Only persons with a neuropathologic diagnosis of intermediate/high AD determined by NIA Reagan and/or NIA-AA criteria were included. A frequency-balanced random sample without replacement was drawn from the NHWD group using a 2:1 age and sex matching scheme with HD. Four brain areas were evaluated: posterior hippocampus, frontal, temporal, and parietal cortices. Sections were stained with antibodies against Aβ (4G8) and phosphorylated tau (AT8). We compared the distribution and semi-quantitative densities for neurofibrillary tangles (NFTs), neuropil threads, core, diffuse, and neuritic plaques. All evaluations were conducted by an expert blinded to demographics and group status. Wilcoxon’s two-sample test revealed higher levels of neuritic plaques in the frontal cortex (p = 0.02) and neuropil threads (p = 0.02) in HD, and higher levels of cored plaques in the temporal cortex in NHWD (p = 0.02). Results from ordinal logistic regression controlling for age, sex, and site of origin were similar. In other evaluated brain regions, semi-quantitative scores of plaques, tangles, and threads did not differ statistically between groups. Our results demonstrate HD may be disproportionately burdened by AD-related pathologies in select anatomic regions, particularly tau deposits. Further research is warranted to understand the contributions of demographic, genetic, and environmental factors to heterogeneous pathological presentations.

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