ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Proteomic analysis in Alzheimer's disease and other dementias: a focus on sex-specific differences.Alzheimer's research & therapy · 2026Article
- Nuclear accumulation of PANK4 in hippocampal astrocytes aggravates cuproptosis in association with mild cognitive impairment in aged mice.Frontiers in aging neuroscience · 2026Article
- DCUN1D5 as a New Biomarker and Regulator of Fatty Acid Metabolism in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Investigating the trivariate reciprocal longitudinal relationships between purpose, loneliness, and cognitive function.The journals of gerontology. Series B, Psychological sciences and social sciences · 2025Article
- CSF proteogenomics implicates novel proteins and humoral immunity in Alzheimer's disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Expanding the horizon of sex-specific proteomic insights in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Extracellular vesicle signatures from eye lavage as novel non-invasive biomarkers for hypoxic ischaemic insult-findings from a neonatal mouse model.Frontiers in medical technology · 2025Article
- Sex- andAlzheimer's & dementia (New York, N. Y.)Article
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Authors and funding
6 authors.
Funding
Abstract
introductionSex differences exist in Alzheimer's disease (AD), but the underlying mechanisms remain unclear.
methodsWe examined brain proteomes profiled from the dorsolateral prefrontal cortex of 770 donors (66.2% female).
resultsProteome-wide differential expression analysis in males and females jointly identified many significant proteins for AD dementia (n = 1228), amyloid beta (n = 1183), tangles (n = 1309), and global cognitive trajectory (n = 2325) at a false discovery rate of <0.05. Sex-stratified analyses also identified many proteins associated with AD or its endophenotypes. Finally, we found 10 proteins with significant sex-by-trait interactions, including one in AD clinical diagnosis (MARCKS), seven in cognitive trajectories (TOGARAM1, PLCD3, SLC22A5, MTFR1L, DCUN1D5, S100A12, and TRIM46), and two in cerebral pathologies (PANK4 and SOS1). DISCUSSION: The 10 proteins with sex interaction in AD cover a range of functions likely relevant for AD pathogenesis, including estrogen response, inflammation, and mitochondrial biology, and their specific roles in AD ought to be studied. Future work should test their potential as sex-specific AD biomarkers. HIGHLIGHTS: At the phenotypic level, we found sex differences in baseline cognitive performance, cognitive trajectories, and AD hallmark pathologies. Proteome-wide differential expression analyses identified many brain proteins associated with AD and its endophenotypes in either sex alone or when considered together. We found 10 brain proteins with significant sex interactions in AD and its endophenotypes, which could be investigated as potential sex-specific biomarkers of AD.
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