Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E ε4 in an Admixed Autopsy Sample
Maison Abu Raya, Claudia Kimie Suemoto, Vitor Ribeiro Paes, Renata Elaine Paraizo Leite, Carlos Augusto Pasqualucci, Michel Satya Naslavsky, Roberta Diehl Rodriguez, Ricardo Nitrini, et al.. JAMA neurology, 2026-04-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Sex and racial or ancestral disparities in Alzheimer disease remain incompletely understood; autopsy studies that examine amyloid, tau, and genetic factors are scarce. Objective To test whether neuritic plaque burden and cognitive outcomes differ by sex and whether sex modifies the effects of apolipoprotein E ε4 (APOEε4), informant-reported race, and African ancestry. Design, setting, and participants This was a cross-sectional study using postmortem neuropathological data from the Biobank for Aging Studies, University of São Paulo, São Paulo, Brazil. A total of 2268 autopsies from a population-based, diverse clinicopathological sample were collected between April 2004 and March 2025. Exposures Sex, informant-reported race (Black, White), African ancestry proportion, and APOEε4 carrier status. Main outcomes and measures Neuritic plaque burden (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] score), and cognitive function (Clinical Dementia Rating-Sum of Boxes [CDR-SB]). Ordinal logistic regression examined association of sex with CERAD scores and 2- and 3-way interactions among sex, race, ancestry, and APOEε4; adjusting for age, education, vascular factors, and Braak stages. Linear models related pathology to CDR-SB, adding copathologies. Results The analysis included 2268 autopsies (median [IQR] age, 74.8 [63.8-83.3] years; 1152 [51% male] and 1116 [49%] female; 802 [35%] Black and 1466 [65%] White; other race groups not included owing to small numbers); female individuals were older than male individuals and more likely to exhibit cognitive impairment (CDR global score ≥0.5). Female individuals had higher plaque burden than male individuals (unadjusted odds ratio [OR], 1.97; 95% CI, 1.67-2.29; P Conclusions and relevance The findings indicate that female sex, APOEε4, and both race and African ancestry were jointly associated with amyloid in this study population. Excess amyloid among women may partly explain their greater tau burden and steeper cognitive decline. These findings highlight the importance of incorporating sex, race, and ancestry into biomarker thresholds, risk stratification, and the design of preventive or disease-modifying trials for Alzheimer disease.
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APA 7th
Raya, M. A., Suemoto, C. K., Paes, V. R., Leite, R. E. P., Pasqualucci, C. A., Naslavsky, M. S., et al. (2026). Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E ε4 in an Admixed Autopsy Sample. JAMA neurology. https://doi.org/10.1001/jamaneurol.2026.0054
Vancouver
Raya MA, Suemoto CK, Paes VR, Leite REP, Pasqualucci CA, Naslavsky MS, et al. Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E ε4 in an Admixed Autopsy Sample. JAMA neurology. 2026. doi:10.1001/jamaneurol.2026.0054. PMID: 41729539.
BibTeX
@article{raya2026-41729539,
author = {Raya, Maison Abu and Suemoto, Claudia Kimie and Paes, Vitor Ribeiro and Leite, Renata Elaine Paraizo and Pasqualucci, Carlos Augusto and Naslavsky, Michel Satya and Rodriguez, Roberta Diehl and Nitrini, Ricardo and others},
title = {{Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E ε4 in an Admixed Autopsy Sample}},
journal = {JAMA neurology},
year = {2026},
doi = {10.1001/jamaneurol.2026.0054},
pmid = {41729539},
url = {https://doi.org/10.1001/jamaneurol.2026.0054}
}
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Key findings
- Results The analysis included 2268 autopsies (median [IQR] age, 74.8 [63.8-83.3] years; 1152 [51% male] and 1116 [49%] female; 802 [35%] Black and 1466 [65%] White; other race groups not included owing to small numbers); female individuals were older than male individuals and more likely to exhibit cognitive impairment (CDR global score ≥0.5).
- Female individuals had higher plaque burden than male individuals (unadjusted odds ratio [OR], 1.97; 95% CI, 1.67-2.29; P Conclusions and relevance The findings indicate that female sex, APOEε4, and both race and African ancestry were jointly associated with amyloid in this study population.
- These findings highlight the importance of incorporating sex, race, and ancestry into biomarker thresholds, risk stratification, and the design of preventive or disease-modifying trials for Alzheimer disease.
Why it matters
In this autopsy study from Brazil, women had higher neuritic plaque burden than men, and the findings indicate that female sex, APOE ε4, and other factors interact in Alzheimer disease pathology. Because it examines brain tissue after death, it helps explain differences in disease biology but does not test any treatment or prevention.
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Study details
- Study designcross-sectional
- Participants2,268
- Effect sizeAdjusted odds ratio for higher neuritic plaque burden, women vs men: 1.65 (95% CI 1.33-2.20; P<.001)
- Evidence strengthModerate
Limitations
Cross-sectional post-mortem data; cognition assessed retrospectively by informant; single Brazilian city; race categories limited to Black and White because of small numbers in other groups.
How this study scored 63/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 62 of the 98 points we could judge it on, which is 63 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,268 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 6 / 6 | Cited 42.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Lea T. Grinberg: h-index 97 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41729539) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 62 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 62 of the 98 points we could judge it on is 63 out of 100. |
| Total | 63 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2026.0054
- PubMed: 41729539
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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