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GLP-1 receptor agonists for Alzheimer's disease: Lessons from trials and translational challenges

4 days 19 hours ago
Alzheimer's disease (AD) is a multifactorial disorder that requires combined therapeutic strategies beyond amyloid clearance. Although GLP-1 receptor agonists show strong mechanistic rationale and supportive epidemiological signals for neuroprotection, large randomized trials in symptomatic AD have yielded negative clinical outcomes and do not support the therapeutic use in AD.
Ramona Stringhi

The nutrition-sleep-circadian axis in age-related neurodegeneration: Cellular mechanisms, metabolic dysfunction, and neuroprotective interventions

4 days 19 hours ago
Advanced age is accompanied by progressive metabolic, nutritional, mitochondrial, and neuroimmune dysregulation, which may increase susceptibility to neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), highlighting the need to identify modifiable mechanisms that influence disease initiation and progression. Increasing evidence indicates that nutrition, sleep, and circadian rhythms function as an interconnected biological network regulating metabolic...
Shaik Basha

Autophagy as a mechanistic link between physical exercise and Alzheimer's disease

4 days 19 hours ago
Alzheimer's Disease (AD), the most prevalent cause of dementia worldwide, is a neurodegenerative disorder that currently has no cure. A growing body of evidence suggests that physical exercise is a potential non-pharmacological strategy in the treatment of AD. Recent findings highlight the involvement of autophagy in the modulatory actions of physical exercise for AD. Here, we present a narrative review of the current knowledge on how exercise impacts AD, specifically focusing on its regulation...
Zhouye Yu

Translating cellular aging clocks into disease risk prediction

4 days 19 hours ago
Ding et al. mapped over 7,000 plasma proteins to more than 40 cell types and developed machine learning aging clocks across 60,000 individuals, demonstrating that cell-type-specific biological aging is heterogeneous, measurable from blood alone, and powerfully predictive of neurodegenerative disease, cancer, and mortality up to 15 years before clinical onset.¹.
Shimaa Heikal

Multimodal brain cell atlas across the adult macaque lifespan

4 days 19 hours ago
High-throughput single-cell omics of non-human primate brain tissue provides a powerful platform to investigate the molecular basis of brain aging. Here, we present a comprehensive transcriptomic and chromatin accessibility atlas of 2,955,873 nuclei from eight brain regions of 23 female cynomolgus macaques spanning the adult lifespan, including exceptionally old individuals. Our analyses reveal dynamic, cell-subtype- and region-specific age-related changes in core brain functions, including...
Xiao Zhang