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Physicists combined human acumen and AI-assisted math to show that a doubted particle interaction is possible after all

Early intervention is the most effective strategy to impede the progression of Alzheimer's disease (AD), depending on the identification of early diagnostic biomarkers. Here, we isolate neuron-derived exosomes (NDEs) from plasma of familial AD (FAD), presymptomatic FAD (pre-FAD), and healthy controls (cognitively normal [CN]), followed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A specific peptide from protein phosphatase 2 regulatory subunit B'β (PPP2R5C)...

Dysfunction of transactive response DNA-binding protein 43 (TDP-43) drives neurodegeneration in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), in part through inducing aberrant RNA splicing. However, whether such mis-splicing yields stable, pathogenic proteins remains unclear. Here, we identify a TDP-43-repressed cryptic exon in Protein kinase N1 (PKN1), designated PKN1-5a1, which is activated in ALS patient brains and introduces a premature termination codon. This aberrant...

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including...

No abstract

The nonreceptor Abelson (Abl) tyrosine kinases have been implicated as key drivers of initiation and progression in Parkinson's disease (PD). Risvodetinib, a potent, brain-penetrant, selective inhibitor of the nonreceptor Abl kinases c-Abl1 and c-Abl2/Arg (collectively, c-Abl), was evaluated in a randomized, double-blind, placebo-controlled phase 2a trial ('the 201 Trial') using once-daily 50 mg, 100 mg, 200 mg or placebo in 137 participants with early, untreated PD. The primary end points in...

Age-related alterations of the haemostatic system substantially contribute to the heightened thrombotic and bleeding risk observed in older adults. While age-associated changes in coagulation have been extensively characterised, impairment of fibrinolysis remains comparatively underexplored, particularly in the context of anticoagulation management. Ageing promotes a hypofibrinolytic milieu through endothelial dysfunction, chronic low-grade inflammation, cellular senescence, and structural...

Solubility regulates protein function, but how it is governed by aging remains elusive. Here, we utilized mass spectrometry to define the relative composition of the soluble and insoluble tissue/organ fractions during mouse aging. In the young, there is a wide (∼100-1,000×) range of insoluble/soluble protein ratios that differ tissue-specifically. With aging, some proteins become relatively more insoluble, while others are conversely regulated or unaffected. Age-related insoluble/soluble changes...

CONCLUSIONS AND IMPLICATIONS: The present findings supported integrating oral health evaluation into nutritional screening in older age and geriatric comprehensive assessment, highlighting the need for interdisciplinary strategies to promote healthy aging.

CONCLUSION: Knowledge synthesized in this review provides insight into the neurobiological mechanisms underlying standing and walking in older adults. The findings of this scoping may lead to developing personalized interventions, such as using non-intensive brain stimulation, to target certain brain activity, which might eventually reduce the risk of falls and disability among older adults.

Selecting the most appropriate model organisms is crucial for studying ageing and ageing-related diseases. While vertebrate aging models offer valuable research feasibility due to their biological complexity and human relevance, their inherent lifespan limitations and high costs significantly restrict their experimental utility. The turquoise killifish (Nothobranchius furzeri, N. furzeri) is a relatively new animal model with the shortest lifespan among vertebrate models. We conducted a...

CONCLUSION: Although hearing care is available to Veterans, multi-level factors influence the delivery of hearing care and management for Veterans with severe hearing loss. Greater attention both in primary and specialty care is needed to ensure tailored treatments are available to Veterans with severe hearing loss across the integrated VA health care system.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including...

Caloric restriction (CR) provides anti-aging benefits but has also been reported to be associated with reduced immune function, and how hematopoietic stem cells (HSCs) potentially contribute to this decline remains unclear. Using lifelong and short-term CR in male mice, we found reducing the energy supply decreases total white blood cell production and shifts hematopoiesis towards myeloid and thrombo-erythroid lineages, prioritizing cells essential for survival (red blood cells, platelets,...

Mutations in genes encoding mitochondrial proteins are increasingly recognized as a major cause of neurodegenerative disorders, owing to the role of mitochondria in neuronal energy metabolism and signaling. Here, we investigate MTNAP1 (mitochondrial nucleoid-associated protein 1) as a novel gene associated with an autosomal recessive neurodevelopmental disorder characterized by progressive cerebral and cerebellar atrophy. Three affected probands from two unrelated families presented with global...

No abstract

Experimental models such as heterochronic parabiosis and heterochronic plasma transfer have profoundly advanced our understanding of systemic aging, demonstrating that circulating factors can influence brain, vascular, and immune aging through cell nonautonomous mechanisms. These preclinical models have revealed that both pro-geronic and anti-geronic signals in blood can modulate neuroinflammation, neurovascular health, and cognitive resilience. However, despite their experimental promise, the...

Tauopathies are neurodegenerative diseases marked by pathological tau aggregation. While disease-specific folds of insoluble tau filaments have been established, it remains unclear whether the smaller, earlier species also differ across tauopathies. Here, we characterize these small tau aggregates from postmortem brain of individuals with Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration, Pick's disease, and healthy controls. Using two complementary...

Heat hormesis describes the beneficial adaptations resulting from transient exposure to mild heat stress, which enhances stress resilience and promotes healthy aging. While heat hormesis is widely observed, much remains to be learned about its molecular basis. This study bridges a critical knowledge gap through a comprehensive multiomic analysis, providing key insights into the transcriptomic and chromatin accessibility landscapes throughout a heat hormesis regimen in Caenorhabditis elegans. We...

Aging is a major risk factor for breast cancer, yet how it shapes tumor development, molecular phenotype, and immune evasion remains incompletely understood. Deciphering how aging influences cancer evolution is critical for improving risk assessment, prevention, and treatment. Here, using a N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model that recapitulates key features of human breast cancer, we integrated bulk and single-cell transcriptomics, whole-exome sequencing, and...