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Exercise alleviates cognitive dysfunction in Alzheimer's disease mice via skeletal muscle-derived extracellular vesicles that enhance plaque clearance by microglia

1 month 3 weeks ago
Exercise confers cognitive benefits in Alzheimer's disease (AD), yet the underlying mechanisms remain incompletely understood. Skeletal muscle functions as an endocrine organ that secretes myokines which affect the homeostasis of extra-muscular organs, including the brain. Here we found that swimming exercise promotes secretion of skeletal muscle-derived extracellular vesicles (SKM-EVs), which are subsequently taken up via pinocytosis by microglia. Gain-of-function and loss-of-function...
Jiaquan Lin

Targeting the FNIP2-SERCA2b axis improves metabolic and mitochondrial defects in Ataxia Telangiectasia

1 month 3 weeks ago
Ataxia telangiectasia (AT) is a rare multisystem disorder caused by the loss of functional ATM protein, leading to immunodeficiency, cancer predisposition, neurodegeneration, diabetes, heart failure, and premature aging. Although ATM's role as a sensor of DNA double-strand breaks (DSBs) is well established, the mechanisms underlying the diverse AT phenotypes remain incompletely understood, with evidence suggesting they extend beyond DSB sensing. Here, we uncover widespread glycogen accumulation...
Maria Vinciguerra

Host Aging Induces a Senescent-Like Phenotype in Neutrophils and Altered Transcriptional Responses to Streptococcus pneumoniae

1 month 3 weeks ago
Aging drives increased susceptibility to respiratory infections by Streptococcus pneumoniae (pneumococci). Polymorphonuclear leukocytes (PMNs) are among the first responders in the lung following pneumococcal infection and are required for bacterial clearance. However, PMN antimicrobial function declines with age. To identify mechanisms underlying this decline, we performed RNA sequencing on PMNs in the lungs of young and old mice following pulmonary infection with S. pneumoniae. We observed...
Michael C Battaglia

The genetic architecture of postoperative delirium after major surgery and its relationship with nonpostoperative neurocognitive conditions: A genome-wide association study

1 month 3 weeks ago
CONCLUSIONS: We identified genetic variants associated with increased risk of postoperative delirium. We also found evidence of shared genetic liability with Alzheimer's disease via APOE, complementing recent large-scale studies in all-cause delirium. If validated, the findings have potential clinical applications, including preoperative risk stratification and early identification of pre-clinical Alzheimer's disease risk.
Richard A Armstrong