Tlr7 drives sex differences in age- and Alzheimer’s disease–related demyelination

Science, Год журнала: 2024, Номер 386(6725)

Опубликована: Ноя. 28, 2024

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 chromosomes gonads in AD. a mouse model demyelination, identified roles modifying microglia oligodendrocyte responses before after myelin loss. an AD-related expressing APOE4, XY heightened interferon (IFN) response tau-induced demyelination. The X-linked gene, Toll-like receptor 7 ( Tlr7 ), regulated sex-specific IFN myelin. Deletion dampened differences while protecting against Administering TLR7 inhibitor mitigated motor impairment male mice, indicating that plays role male-biased type I Interferon aging-

Язык: Английский

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How Is the X Chromosome Involved in Alzheimer Disease?

JAMA Neurology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Язык: Английский

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X‐chromosome-wide association study for Alzheimer’s disease

Molecular Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 4, 2024

Abstract Due to methodological reasons, the X-chromosome has not been featured in major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) 115,841 AD cases or proxy cases, including 52,214 clinically-diagnosed 613,671 controls. We considered three approaches account for different inactivation (XCI) states females, i.e. random XCI, skewed escape XCI. did detect any significant signals (P ≤ 5 × 10 − 8 ) but identified seven X-chromosome-wide loci 1.6 6 ). The index variants were common Xp22.32, FRMPD4, DMD Xq25 loci, rare WNK3 , PJA1 DACH2 loci. Overall, well-powered XWAS found no risk factors non-pseudoautosomal region X-chromosome, it suggestive warranting further investigations.

Язык: Английский

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The Contribution of the Renin-Angiotensin System to Alzheimer’s Disease

Current topics in behavioral neurosciences, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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