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CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer's disease
CHI3L1/YKL-40 is an astrocyte-secreted glycoprotein recognized as a biomarker of CNS inflammation and implicated in Alzheimer's disease (AD) cognitive decline. However, its precise pathological role remains unclear. Here, we investigate CHI3L1's function and its therapeutic potential in AD using both human induced pluripotent stem cell-derived neurogenesis models and in vivo conditional AD mouse models, with astrocyte-specific CHI3L1 knockout, alongside 5XFAD mice. Our data reveal that CHI3L1...
Multiomic identification of senescent stem cell populations critical for osteoarthritis progression and therapy in subchondral bones
Osteoarthritis (OA) is a challenging degenerative joint disease with limited treatment options. Subchondral bone plays a critical role in maintaining joint homeostasis and influencing OA progression. Here, we investigated the role of senescence in mesenchyme-derived stem/progenitor cells (MDSPCs) during OA progression, aiming to identify potential therapeutic targets. Histopathological evaluations and bioinformatic analyses of OA samples from both humans and mice revealed that EGFR^(+) MDSPCs...
Effectiveness of mindfulness-based interventions on inflammaging: a systematic review and meta-analysis
Mindfulness cultivates awareness, presence, and non-judgmental acceptance, enhancing overall well-being. Inflammaging, linking age and aged-related diseases, manifests through heightened levels of IL-6, TNF-α, and CRP, impacting aging indicators like TA, TL, PWV, and FMD. To assess how mindfulness-based interventions (MBIs) affect inflammaging, a search was conducted in PubMed, Web of Science, Cochrane Central Register, and ProQuest Dissertation & Theses Global up to March 2024. Criteria...
GABA, Glx, and GSH in the cerebellum: their role in motor performance and learning across age groups
INTRODUCTION: The cerebellum is essential for motor control and learning, relying on structural and functional integrity. Age-related atrophy leads to Purkinje cell loss, but subtle neurochemical changes in GABA, Glx (glutamate + glutamine), and glutathione (GSH) may precede degeneration and contribute to motor decline.
Daily briefing: How the brain boots up from sleep to wakefulness
Sex at birth is not always random — mum’s age and genetics can play a part
Should I tell anyone that I suspect misconduct in a paper I’m reviewing?
Class of 2025: five PhD students reveal realigned priorities in wake of COVID and cuts
Pathology-oriented multiplexing enables integrative disease mapping
This ancient mega-predator was built for stealth
Asia’s haze affects ice and weather on the Frozen Continent
To the Moon and quack: Books in brief
Fearful of AI-generated grant proposals, NIH limits scientists to six applications per year
Some critics of the new policy say the cap could hinder researchers in need of funding
U.S. research community says new indirect cost model is still too complicated
Proposed changes to avert huge cuts in reimbursement get pushback at town hall
Why do some moms have more boys than girls—or vice versa? New study provides clues
Researchers find that certain genetic variants and mother’s age may have an impact on the sex of her children
A new kind of telescope is set to search for mysterious fast radio bursts
Radio telescopes usually have giant dishes, but not these all-sky antenna arrays
Russian scientists’ international collaborations to be vetted by security services under new law
Move will have a chilling effect and further isolate the country from the global scientific community, researchers say
Insights into the toxic effects of micro-nano-plastics on the human brain and their relationship with the onset of neurological diseases: A narrative review
The intensive production and use of plastics, poor biodegradability and inadequate recycling have caused excessive and alarming environmental pollution. This has led to the inevitable intake by humans, through different routes, of small plastic particles, the micro and nano-plastics (MNPs) with sizes ranging from nanometers (<1000 nm) to micrometers (from 5 mm to 1 µm). MNPs can cause harmful effects in human tissues and organs, contributing to the early onset of aging and various age-related...
AI-guided patient stratification improves outcomes and efficiency in the AMARANTH Alzheimer's Disease clinical trial
Alzheimer's Disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, we demonstrate that our robust and interpretable AI-guided tool (predictive prognostic model, PPM) enhances precision in patient stratification, improving outcomes and decreasing sample size for a AD clinical trial. The AMARANTH trial of lanabecestat, a BACE1 inhibitor, was deemed futile, as treatment did not change cognitive outcomes, despite...
Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes
Secretory proteins aggregate into non-soluble dense-core granules in recycling endosome-like compartments prior to regulated release. By contrast, aberrantly processed, secreted amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) form pathological extracellular amyloidogenic aggregations in late-stage Alzheimer's disease (AD). By examining living Drosophila prostate-like secondary cells, we show that both APP and Aβ peptides affect normal biogenesis of dense-core granules. These...