Why women’s brains are more resilient: it could be their ‘silent’ X chromosome

Nature, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Язык: Английский

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Why women experience Alzheimer’s disease differently from men

Nature, Год журнала: 2025, Номер 640(8059), С. S14 - S17

Опубликована: Апрель 16, 2025

Язык: Английский

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Cell-Type-Specific Transposable Element Demethylation and TAD Remodeling in the Aging Mouse Brain

Опубликована: Янв. 1, 2025

Язык: Английский

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Single Cell Landscape of Sex-specific Drivers of Alzheimer’s Disease

Опубликована: Апрель 22, 2025

Background Sex differences in Alzheimer’s disease (AD) have been documented for decades, and many sex-specific molecular contributors to AD discovered through bulk omics analysis of brain tissues. RNA sequencing (RNAseq) at single cell resolution provides an opportunity characterize transcript associations with a type-specific matter. Here, we investigated gene expression neuropathology cognitive manifestation (endophenotypes) leveraging large single-nucleus transcriptomic dataset consisting 1.64 million nuclei from dorsolateral prefrontal cortex (DLPFC) tissue 424 unique donors the Religious Orders Study Memory Aging Project (ROS/MAP; Knowledge Portal syn2580853). Methods ROS/MAP RNAseq data (snRNA-seq) were processed rigorous pipeline. In total, eight major types DLPFC identified. We first performed sex-stratified sex-interaction association analyses by fitting negative binomial mixed models relation β-amyloid load (Aβ), paired helical filament tau tangle density (tau), global performance last visit, longitudinal trajectory. then conducted gene-set enrichment identify functional signaling pathways enriched associations. Lastly, compared differential patterns intercellular communication profiles between sexes diagnostic groups among types. For replication, examined using snRNA-seq derived tissue-derived independent set 84 The Seattle Disease Brain Cell Atlas (SEA-AD) study. Results 68% participants female, 52% diagnosed dementia. identified several disease-dependent or sex-dependent subpopulations. Then 2,660 involving 2,110 genes Aβ (51%), (21%), (29%). 60% female-specific Aβ, 49% male-specific tau. vast majority (93%) female protective neurons, most (76%) risk glial cells. Nine replicated SEA-AD cohort, including ADGRV1 OR3A3 Aβ; IFI27L1 , LYRM1 STAP2 TSTD2 tau; PDYN cognition; TMEM50B decline. All except observed neurons. Furthermore, preponderance neurons was also recapitulated cohort. Sex-specific immune, inflammation, damage-related stress response pathways, microglia presented pathways. Finally, six ITGB1-mediated microglia-specific incoming signals that may play role accumulation. Conclusion Our study highlights transcriptome-wide, single-cell landscape delineate full scope associations, expression, pathway, cell-cell network changes each type, while identifying replicating help direct future mechanistic studies.

Язык: Английский

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Le chromosome X : un bouclier contre le déclin cognitif ?

Cerveau & Psycho, Год журнала: 2025, Номер n° 176(5), С. 8 - 8

Опубликована: Апрель 8, 2025

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