Aggregator

Patients who got shots of mRNA before starting a type of cancer immunotherapy lived much longer

Study pinpoints likely date for a massive earthquake on the Puerto Rico Trench—and highlights an underappreciated regional hazard

Unusual hiring process raises fears of political favoritism

Age-related decline in motor control, manifesting as impaired posture, gait, and slowed movement execution, significantly diminishes the quality of life in older adults. These functional deficits are associated with alterations in neurophysiological data, which are analyzed using advanced techniques including spectral analysis, complexity measures, and functional connectivity network analysis. These methodologies provide valuable insights into the neurobiological mechanisms underpinning...

Direct care workers in long-term care settings are essential to provide care for older adults and people with disabilities who have daily needs. There is an increasing demand for an adequately sized and well-prepared direct care workforce to support people living with dementia due to its rising prevalence. However, a lack of standardized policies and data leaves researchers and policymakers with little evidence to guide the development and refinement of workforce policies. The National Institute...

Aging increases vulnerability to cognitive decline after repetitive mild traumatic brain injury (rm-TBI), yet mechanisms linking age-related factors to neurodegeneration remain poorly understood. This study investigated how brain-derived exosomes from aged mice (A-Exo) worsen rm-TBI outcomes. In a murine rm-TBI model, intranasal A-Exo administration significantly exacerbated spatial memory deficits and hippocampal neuronal apoptosis compared to brain-derived exosomes from young mice (Y-Exo) or...

Age-related renal impairment often occurs insidiously and has become an important cause of chronic renal failure, especially when individuals with other chronic diseases. However, there is lack of effective treatments. Research on diabetic patients has revealed that empagliflozin (EMPA), one of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, exhibits a distinct protective effect on aging kidneys. EMPA has been shown to improve renal fibrosis and ameliorate inflammatory cytokines, including...

We previously reported that T96K is a gain-of-function mutation in TREM2 based on its ability to increase ligand-dependent activation. Here, we show that TREM2^(T96K) increases risk for Alzheimer's disease (AD) in a whole-genome sequencing dataset comprised of family-based and case-control samples. Trem2^(T96K) also reduced clustering of microglia around β-amyloid (Aβ) plaques exclusively in female 5xFAD mice. Furthermore, T96K decreased levels of soluble Trem2 in female 5xFAD mice and human...

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are major public health challenges. Current treatments are only symptomatic and do not address the underlying pathogenic genetic mechanisms. The development of the CRISPR/Cas genome editing tool has increased possibilities for targeted repair of pathological mutations. CRISPR/Cas9, Cas12, and Cas13 systems enable targeted editing and transcriptome modulation in various preclinical...

Cu/Zn superoxide dismutase 1 (SOD1) is essential for maintaining neural health. Its functions include modulating metabolism, maintaining redox balance, regulating transcription, besides eliminating superoxide radicals, which are achieved through various post-translational modifications (PTMs). Consequently, unusual PTMs in SOD1 can impair its functionality and stability, leading to the accumulation of misfolded SOD1 and the increase of oxidative stress markers, hallmarks of Amyotrophic Lateral...

Patient-specific, human-based cellular models integrating a biomimetic blood-brain barrier, immune, and myelinated neuron components are critically needed to enable accelerated, translationally relevant discovery of neurological disease mechanisms and interventions. To construct a human cell-based model that includes these features and all six major brain cell types needed to mimic disease and dissect pathological mechanisms, we have constructed, characterized, and utilized a multicellular...

Alzheimer's disease is a neurodegenerative disorder with a variable rate of progression. Predictive tools that can leverage the available modalities of data in any setting to predict the progression of the disease will benefit clinicians and patients alike. However, most of the tools lack the ability to quantify the uncertainty and do not provide the reasoning behind the predictions. In this work, we propose a novel Bayesian Encoder-Decoder GRU (BEND-GRU) framework to predict a patient's...

Tau misfolding into β-sheet-rich filaments and subsequent recruitment of monomeric tau are central to Alzheimer's disease (AD) pathogenesis. While cryo-EM has resolved the conformation of the AD tau core, the structural features conferring biological activity remain unclear. Here, we investigated how tau filament core structure and post-translational modifications influence seeding capacity in neurons and mice. Our findings show that although filament structure impacts seeding, the AD tau core...