ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
CSF proteomic profiling with amyloid and tau pathology identifies distinctive sex-specific alteration of multiple proteins involved in Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Proteomic analysis in Alzheimer's disease and other dementias: a focus on sex-specific differences.Alzheimer's research & therapy · 2026Article
- APOE-stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CSF proteomic profiling with amyloid and tau pathology identifies distinctive sex-specific alteration of multiple proteins involved in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Leveraging multiomic approaches to elucidate mechanisms of heterogeneity in Alzheimer's disease: Neuropsychiatric symptoms, co-pathologies, and sex differences.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Connecting genomic and proteomic signatures of amyloid burden in the brain.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
18 authors.
Funding
Abstract
introductionIn Alzheimer's disease (AD), females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited.
methodsWe comprehensively examined 6162 proteins in cerebrospinal fluid (CSF) from 2496 participants to identify sex-specific proteomic alteration by CSF amyloid beta (Aβ)42 and phosphorylated tau (p-tau) levels.
resultsWe identified and replicated 68 male-specific and 116 female-specific proteins associated with Aβ42 and/or p-tau levels. Apolipoprotein E ε4 carrier status modified sex-specific alterations of multiple proteins including S100A9 and NEFL for Aβ42 and MAPK9 and MAPKAPK2 for p-tau. Male-specific proteins, enriched in microglia, were involved in activating innate immune response. The male network exhibited direct connections among 30 proteins and highlighted MAPKAPK2 as a hub. Female-specific proteins, enriched in endothelial cells, were involved in regulating protein metabolic process. The female network exhibited direct connections among 43 proteins and highlighted CSNK2A2 and PRKCA as hubs. DISCUSSION: Our findings provide insights into mechanistic understanding of sex differences in AD risk. HIGHLIGHTS: Our proteomic study of 6162 proteins (targeted by 7006 aptamers) in cerebrospinal fluid (CSF) from 2496 participants identified and replicated 68 male-specific and 116 female-specific proteins associated with cerebrospinal fluid amyloid beta 42 and/or phosphorylated tau levels. Male-specific proteins, enriched in microglia, were involved in activation of innate immune response. The male network highlighted MAPKAPK2 involved in chronic neuronal neuroinflammation as a hub. Female-specific proteins, enriched in endothelial cells, were involved in regulation of protein metabolic process and response to external stimuli. The female network highlighted PRKCA regulating synaptic plasticity and CSNK2A2 protein involved in neuroplasticity as hubs.
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