Evidence mapPaperPMID 41708549Full record

ArticleGeroScience2026

Sex and APOE genotype specific brain regional vulnerability to Alzheimer's Disease.

Qi Zeng, Minghui Wang, Erming Wang, Xianxiao Zhou, Peng Xu, Vahram Haroutunian, Dongming Cai, Bin Zhang, Members of the Alzheimers Disease Neuroimaging Initiative

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Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Qi ZengDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place , New York, NY, 10029, USA.
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place , New York, NY, 10029, USA.
Erming WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place , New York, NY, 10029, USA.
Xianxiao ZhouDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place , New York, NY, 10029, USA.
Peng XuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place , New York, NY, 10029, USA.
Vahram HaroutunianNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
Dongming CaiN. Bud Grossman Center for Memory Research and Care, Department of Neurology, University of Minnesota, Minneapolis, MN, 55455, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place , New York, NY, 10029, USA. bin.zhang@mssm.edu.ORCID http://orcid.org/0000-0002-9549-5653
Members of the Alzheimers Disease Neuroimaging Initiative

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) disproportionately affects women and carriers of the apolipoprotein E ε4 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) integrity during disease progression. We integrated diffusion MRI and matched blood transcriptomic data to investigate these interactions and their underlying biological mechanisms. WM microstructure was quantified using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), and regional vulnerability was assessed with a composite vulnerability score (CVS) derived from associations between diffusion features and AD severity across clinical traits in each of the four sex-APOE groups (female or male, with or without APOE4). Brain parcellation with the Eve atlas revealed regions consistently affected across sex-APOE groups (e.g., parahippocampal and superior temporal gyri) and regions specific to individual groups (e.g., the cingulum in females with APOE4 and the middle frontal gyrus in males without APOE4). Gene co-expression network analysis of the matched blood expression data identified gene subnetworks linked to group-specific regional vulnerability, including a muscle tissue morphogenesis module regulated by NEURL1B and HIST1H2BN associated with middle frontal gyrus vulnerability. These findings demonstrate that sex and APOE genotype jointly shape region-specific WM vulnerability and its molecular signatures in AD. Understanding these interactions provides novel mechanistic insights and may inform precision approaches to drug development, biomarker discovery, and clinical trial design for AD.

Indexed as

Alzheimer’s diseaseApolipoprotein EDiffusion tensor imaging, gene coexpression network analysisSex

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.