ArticleCells2023
Novel Isolation Method Reveals Sex-Specific Composition and Neurotoxicity of Small Extracellular Vesicles in a Mouse Model of Alzheimer's Disease.
Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- A Novel Reporter Mouse for Astrocyte-Derived Extracellular Vesicles Reveals Enrichment of Cargo at Neuronal Mitochondria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- A novel reporter mouse for astrocyte-derived extracellular vesicles reveals trafficking of cargo to neuronal mitochondria.bioRxiv : the preprint server for biology · 2026Article
- Ceramide-rich extracellular vesicles as pathogenic biomarkers in traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles.Journal of extracellular vesicles · 2024Article
- Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer's Disease Pathology and Diagnosis.Antioxidants (Basel, Switzerland) · 2024Review
- Abnormal Regulation of Mitochondrial Sphingolipids during Aging and Alzheimer's Disease.ASN neuro · 2024Article
- Unraveling the Multifaceted Role of the Golgi Apparatus: Insights into Neuronal Plasticity, Development, Neurogenesis, Alzheimer's Disease, and SARS-CoV-2 Interactions.Brain sciences · 2023Review
- Inhibition of acid sphingomyelinase reduces reactive astrocyte secretion of mitotoxic extracellular vesicles and improves Alzheimer's disease pathology in the 5xFAD mouse.Acta neuropathologica communications · 2023Article
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Authors and funding
10 authors.
Funding
Abstract
We developed a new method to isolate small extracellular vesicles (sEVs) from male and female wild-type and 5xFAD mouse brains to investigate the sex-specific functions of sEVs in Alzheimer's disease (AD). A mass spectrometric analysis revealed that sEVs contained proteins critical for EV formation and Aβ. ExoView analysis showed that female mice contained more GFAP and Aβ-labeled sEVs, suggesting that a larger proportion of sEVs from the female brain is derived from astrocytes and/or more likely to bind to Aβ. Moreover, sEVs from female brains had more acid sphingomyelinase (ASM) and ceramide, an enzyme and its sphingolipid product important for EV formation and Aβ binding to EVs, respectively. We confirmed the function of ASM in EV formation and Aβ binding using co-labeling and proximity ligation assays, showing that ASM inhibitors prevented complex formation between Aβ and ceramide in primary cultured astrocytes. Finally, our study demonstrated that sEVs from female 5xFAD mice were more neurotoxic than those from males, as determined by impaired mitochondrial function (Seahorse assays) and LDH cytotoxicity assays. Our study suggests that sex-specific sEVs are functionally distinct markers for AD and that ASM is a potential target for AD therapy.
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