ArticleFrontiers in aging neuroscience2022
Sex-specific transcriptional rewiring in the brain of Alzheimer's disease patients.
Article in Frontiers in aging neuroscience, 2022. 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, 13 citations in OpenAlex.
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sex-dependent grey matter atrophy in Alzheimer's disease progression.Brain communications · 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
- Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Regulatory mechanisms of neuro inflammation from a gender perspective: interactions among astrocytes, sex hormones, and the gut-brain axis.Frontiers in aging neuroscience · 2025Article
- Association between gynecologic cancer and Alzheimer's disease: a bidirectional mendelian randomization study.BMC cancer · 2024Article
- Article
- Co-Expression Network Analysis Identifies Molecular Determinants of Loneliness Associated with Neuropsychiatric and Neurodegenerative Diseases.International journal of molecular sciences · 2023Article
- Biological and Clinical Implications of Sex-Specific Differences in Alzheimer's Disease.Handbook of experimental pharmacology · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sex-specific differences may contribute to Alzheimer's disease (AD) development. AD is more prevalent in women worldwide, and female sex has been suggested as a disease risk factor. Nevertheless, the molecular mechanisms underlying sex-biased differences in AD remain poorly characterized. To this end, we analyzed the transcriptional changes in the entorhinal cortex of symptomatic and asymptomatic AD patients stratified by sex. Co-expression network analysis implemented by SWItchMiner software identified sex-specific signatures of switch genes responsible for drastic transcriptional changes in the brain of AD and asymptomatic AD individuals. Pathway analysis of the switch genes revealed that morphine addiction, retrograde endocannabinoid signaling, and autophagy are associated with both females with AD (F-AD) and males with (M-AD). In contrast, nicotine addiction, cell adhesion molecules, oxytocin signaling, adipocytokine signaling, prolactin signaling, and alcoholism are uniquely associated with M-AD. Similarly, some of the unique pathways associated with F-AD switch genes are viral myocarditis, Hippo signaling pathway, endometrial cancer, insulin signaling, and PI3K-AKT signaling. Together these results reveal that there are many sex-specific pathways that may lead to AD. Approximately 20-30% of the elderly have an accumulation of amyloid beta in the brain, but show no cognitive deficit. Asymptomatic females (F-asymAD) and males (M-asymAD) both shared dysregulation of endocytosis. In contrast, pathways uniquely associated with F-asymAD switch genes are insulin secretion, progesterone-mediated oocyte maturation, axon guidance, renal cell carcinoma, and ErbB signaling pathway. Similarly, pathways uniquely associated with M-asymAD switch genes are fluid shear stress and atherosclerosis, FcγR mediated phagocytosis, and proteoglycans in cancer. These results reveal for the first time unique pathways associated with either disease progression or cognitive resilience in asymptomatic individuals. Additionally, we identified numerous sex-specific transcription factors and potential neurotoxic chemicals that may be involved in the pathogenesis of AD. Together these results reveal likely molecular drivers of sex differences in the brain of AD patients. Future molecular studies dissecting the functional role of these switch genes in driving sex differences in AD are warranted.
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