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. 2023 Jun 29;11(1):105.
doi: 10.1186/s40478-023-01574-1.

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

Rebeca Scalco  1 , Naomi Saito  2 , Laurel Beckett  2 , My-Le Nguyen  1 , Emily Huie  1 , Hsin-Pei Wang  1 , Delaney A Flaherty  3 , Lawrence S Honig  4 , Charles DeCarli  5 , Robert A Rissman  6 , Andrew F Teich  3   4 , Lee-Way Jin  1 , Brittany N Dugger  7
Affiliations

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

Rebeca Scalco et al. Acta Neuropathol Commun. .

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.

Keywords: Alzheimer disease research centers; Autopsy; Dementia; Disparities; Histology; LatinX; Latino; Neurodegeneration; Tauopathy.

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Conflict of interest statement

This project was primarily made possible by grants from the National Institute on Aging (NIA) of the National Institutes of Health (NIH) under Award Numbers R01AG062517, P30AG072972, P30AG062429, P50AG008702, P30AG066462. BND: receives funding by grants from the National Institute on Aging (NIA) of the National Institutes of Health (NIH) under Award Numbers P30AG072972, U01AG061357-S1, R01AG052132, R01AG056519, and R01AG062517. She serves on the external advisory board for the Alzheimer’s Disease Center at USC, and as a committee member for the ADRC neuropathology committee and the College of American Pathologists Neuropathology committee. She has no conflicts of interest to declare related to this project. LB: has received support over the last 48 months from payments to her institution from U01AG024904 (Dr. Weiner, UCSF/NCIRE), R01AG062517 (Dr. Dugger), B639943 (Dr. Coleman), and the National Institute of Justice 2014-R2-CX-0012 (Dr. Wintemute). She has served on the external advisory boards for Alzheimer’s Disease Centers at UCSD, Washington University, University of Pittsburgh, and Data and Safety Monitoring Boards for NIH-funded clinical trials (UCSF), and as an external advisory board member for the LEADS study, all paid directly to her. She has no other support or conflicts of interest to declare. RR has received support from AG058252, AG073979, AG051848 to RAR and biomarker. Other authors report no conflicts of interest relevant to this project.

Figures

Fig. 1
Fig. 1
Participant flow diagram summarizing cohort selection, screening, random selection and matching of cases, and inclusion and exclusion criteria in the study
Fig. 2
Fig. 2
A visualization comprising of a combination of violin and box plots was used to depict the distribution of various pathologies (cored plaques: CPs, diffuse plaques: DPs, neuritic plaques: NPs, neuropil threads: NTs, and neurofibrillary tangles: NFTs) in three specific brain areas-frontal, temporal, and parietal cortices. The violin plots were used to display the distribution of the data, while the boxes indicate the range between the first and third quartiles. The bold horizontal line inside the boxes represents the median value. Additionally, the whiskers extend beyond the upper and lower limits of the box and indicate the range of data within 1.5 times the length of the box
Fig. 3
Fig. 3
Examples of the histopathologic densities of tau-deposits and corresponding overall regional density scores (for neuropil threads: NTs, and neurofibrillary tangles: NFTs- lower left corner in each image) in three brain regions (frontal, temporal, and parietal cortices). Cases were selected based on heritage group within Hispanic decedents and non-Hispanic White decedents, having similar age at death, gender, and AD likelihood (ADNC = Alzheimer disease neuropathologic change). Scale bar = 50 μm
See this image and copyright information in PMC

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