Nature Aging, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Язык: Английский
Nature Aging, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Язык: Английский
Процитировано
1
Nature, Год журнала: 2025, Номер unknown
Опубликована: Март 5, 2025
Язык: Английский
Процитировано
0
Nature, Год журнала: 2025, Номер 640(8059), С. S14 - S17
Опубликована: Апрель 16, 2025
Язык: Английский
Процитировано
0
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
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
Процитировано
0
Cerveau & Psycho, Год журнала: 2025, Номер n° 176(5), С. 8 - 8
Опубликована: Апрель 8, 2025
Процитировано
0
Nachrichten aus der Chemie, Год журнала: 2025, Номер 73(5), С. 77 - 79
Опубликована: Апрель 30, 2025
Abstract Geschlechter‐Unterschiede sind in der Medizin relevant, etwa im Immunsystem, bei Herzinfarkten und Wirkung von Medikamenten. Und sie zu lange vernachlässigt worden. Es bleibt noch einiges verbessern, bis jede:r die richtige Behandlung bekommt.
Процитировано
0
Nature Aging, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Язык: Английский
Процитировано
0