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Dysfunction of the glymphatic system has been proposed as a mechanistic link between sleep disruption and Alzheimer's disease (AD). In animal models, glymphatic impairment alone can drive AD pathology. Whether this system clears amyloid beta (Aβ) and tau in humans remains unknown. In a randomized crossover trial with 39 participants, we found that glymphatic clearance during normal sleep increased morning plasma levels of AD biomarkers compared to sleep deprivation. Participants underwent...

Meningeal immune cells monitor the central nervous system (CNS) and influence neuroinflammation in mice, but the human leptomeningeal immune landscape and the changes that occur in this immunological niche in neurodegeneration remain underexplored. Here we performed single-cell RNA and T cell receptor (TCR) sequencing of 99,625 high-quality immune cells from 57 leptomeninges and brain samples from donors with Alzheimer's disease (AD), amyotrophic lateral sclerosis and Parkinson's disease and...

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CONCLUSION: To our knowledge, this study is the first to characterize and correlate the diversity of both the OM and GM with systemic FFA and cytokine profiles in a cohort of healthy adults, highlighting the critical role of age in shaping microbiome composition and associated metabolites. Integrating microbiota profiling with serum FFA and cytokine measurements enhances our understanding of how the microbiome may influence health and disease risk across the adult lifespan.

CONCLUSIONS AND IMPLICATIONS: Referral decisions for post-acute care are influenced by individual-, hospital-, and community-level factors. As the use of HHC continues to grow, greater attention is needed to how these decisions are made to ensure equitable access to preferred and appropriate care for older adults.

The Drosophila proventriculus is a bulb-shaped structure at the juncture of the foregut and the midgut, which plays important roles in ingestion, peritrophic membrane synthesis, and the immune response to oral pathogens. A previous study identified a population of cells in the proventriculus which incorporate bromodeoxyuridine (BrdU), a marker of DNA synthesis, and proposed that these cycling cells are multipotent stem cells that replace dying cells elsewhere in the tissue. Here, we...

Exposure to non-relational trauma, such as serious accidents, war or life-threatening illness, is linked to poor mental and physical health. Its relationship with biological ageing markers, however, remains underexplored. This study's aim was to examine associations between non-relational trauma and multiple biological ageing markers, and to assess whether associations vary by trauma burden, trauma type and sex. We analysed UK Biobank data from 152,863 participants (mean age = 56.4 years; 56.5%...

Epigenetic remodeling is a hallmark of aging, yet which epigenetic layers are most affected during aging-and the extent to which they are interrelated-is not well understood. Here, we perform a comprehensive analysis of epigenetic aging encompassing 6 histone marks and DNA methylation measured across 12 tissues from > 1000 humans and mice. We identify a synchronized pattern of age-related changes across these epigenetic layers, with all changes converging upon a common set of genes. Notably, an...