Peer-reviewed veterinary case report
drives sex differences in age- and Alzheimer's disease-related demyelination.
- Journal:
- Science (New York, N.Y.)
- Year:
- 2024
- Authors:
- Lopez-Lee, Chloe et al.
- Affiliation:
- Helen and Robert Appel Institute for Alzheimer's Disease Research · United States
- Species:
- rodent
Abstract
Alzheimer's disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss. In an AD-related mouse model expressing APOE4, XY sex chromosomes heightened interferon (IFN) response and tau-induced demyelination. The X-linked gene, Toll-like receptor 7 (), regulated sex-specific IFN response to myelin. Deletion ofdampened sex differences while protecting against demyelination. Administering TLR7 inhibitor mitigated tau-induced motor impairment and demyelination in male mice, indicating thatplays a role in the male-biased type I Interferon IFN response in aging- and AD-related demyelination.
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Search related cases →Original publication: https://pubmed.ncbi.nlm.nih.gov/39607927/