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Liver exerkine reverses aging- and Alzheimer's-related memory loss via vasculature

2 weeks 4 days ago
Blood factors transfer the benefits of exercise to the aged brain independent of physical activity. Here, we show that the liver-derived exercise factor (exerkine) glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer's-related memory loss by targeting the brain vasculature. GPLD1 has the potential to cleave over 100 putative GPI-anchored proteins, necessitating the identification of downstream targets that mediate cognitive...
Gregor Bieri

Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury

2 weeks 4 days ago
Insulating sheaths of myelin accelerate neuronal communication in the mammalian brain. Oligodendrocytes that produce myelin are generated throughout life to gradually increase myelin coverage, but these dynamics have not been defined brain-wide across the lifespan. We developed a cellular mapping pipeline involving tissue clearing, lightsheet microscopy, and AI-assisted analysis to identify the precise location of millions of oligodendrocytes and assess regional myelin density in the mouse...
Yu Kang T Xu

Vulnerability of short-term memory in a mouse model of Alzheimer's disease

2 weeks 4 days ago
Interference from distracting stimuli renders short-term memory vulnerable. While behavioral evidence suggests short-term memory deficits in Alzheimer's disease (AD), the underlying neural mechanisms remain poorly understood. Using a mouse model of AD (APP-KI), we identified increased susceptibility of short-term memory to sensory perturbations. Simultaneous two-photon calcium imaging across eight cortical regions during a delayed-response task showed that distractors disrupted neural...
Chunyue Li

Deep learning models identify brain changes during the progression of Alzheimer's disease

2 weeks 4 days ago
Alzheimer's disease (AD) is an irreversible neurodegenerative disorder whose progression is closely associated with time. However, most diagnostic models are based on single time-point data, overlooking longitudinal disease characteristics. Structural magnetic resonance imaging (sMRI) has been widely utilized in the study of AD. To address the need for multi-time series analysis in longitudinal AD research and the integration of features from different brain tissues, we propose a Multi-Branch...
Jinhui Sun

Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks

2 weeks 4 days ago
Predicting not just if, but also when, cognitively unimpaired individuals are likely to develop onset of Alzheimer's disease (AD) symptoms would be useful to clinical trials and, eventually, clinical practice. Although clock models based on amyloid and tau positron emission tomography have shown promise in predicting the onset of AD symptoms, a model based on plasma biomarkers would be more accessible. Using longitudinal plasma %p-tau217 (the ratio of phosphorylated to non-phosphorylated tau at...
Kellen K Petersen

We wait for disease to shout-What if we listened when biology whispered?

2 weeks 4 days ago
Most diseases are not caused by large-effect single factors but by the cumulative impact of small, context-dependent perturbations arising from genetic variants, personal behavior, or environmental exposures, a phenomenon we term the "long tail" of biology. Early disease signals often differ from late-stage biomarkers and evolve across demographic, lifestyle, and environmental contexts. Shifting medicine from reactive treatment to proactive health requires detecting and interpreting these...
Noa Rappaport

Liver exerkine reverses aging- and Alzheimer's-related memory loss via vasculature

2 weeks 4 days ago
Blood factors transfer the benefits of exercise to the aged brain independent of physical activity. Here, we show that the liver-derived exercise factor (exerkine) glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer's-related memory loss by targeting the brain vasculature. GPLD1 has the potential to cleave over 100 putative GPI-anchored proteins, necessitating the identification of downstream targets that mediate cognitive...
Gregor Bieri

Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury

2 weeks 4 days ago
Insulating sheaths of myelin accelerate neuronal communication in the mammalian brain. Oligodendrocytes that produce myelin are generated throughout life to gradually increase myelin coverage, but these dynamics have not been defined brain-wide across the lifespan. We developed a cellular mapping pipeline involving tissue clearing, lightsheet microscopy, and AI-assisted analysis to identify the precise location of millions of oligodendrocytes and assess regional myelin density in the mouse...
Yu Kang T Xu

Characteristics of the Long-Term Care Data Cooperative: A New Resource for Research on Outcomes in Long-Term Care

2 weeks 4 days ago
CONCLUSIONS: The LTC Data Cooperative offers novel EHR data capturing clinical measures not available in the Minimum Data Set or claims data on a SNF resident population that is comparable to the national population. Studies using these data can generate evidence to inform and improve clinical care and outcomes for older adults in the SNF setting.
Stephanie M Kissam

Mixed-matrix membranes with molecular recognition windows for selective helium extraction from natural gas

2 weeks 4 days ago
Mixed-matrix membranes (MMMs) with high chain packing density by incorporating soluble macrocycle compounds represent a promising class of materials for gas separation. However, achieving the ultra-high selectivity (He/CH(4) > 1000) for helium extraction from natural gas with ultra-low helium content remains a formidable challenge, especially for Matrimid membranes, which are commercially available but exhibit relatively low permeability and moderate selectivity. Herein, the cyclic Cyclen with...
Wen He

Young blood-induced rejuvenation of neurovascular coupling involves endothelial IGF-1/IGF-1R signaling: evidence from heterochronic parabiosis using endothelial IGF-1R deficient and systemic IGF-1 knockdown mice

2 weeks 4 days ago
Aging is accompanied by progressive impairment of neurovascular coupling (NVC), the mechanism that matches local cerebral blood flow to neuronal activity, contributing to cognitive decline and the development of vascular cognitive impairment and dementia. Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore NVC in aged mice, suggesting that circulating factors can rejuvenate cerebrovascular function. Yet, the molecular mediators responsible for this...
Rafal Gulej

Are levels of DHEAS indicative of subjective health - results of the population-based longitudinal CARLA study

2 weeks 4 days ago
Subjective and objective markers are important in describing healthy aging, yet little is known about their relationships. This study analysed the time-dependent association of dehydroepiandrosterone sulfate (DHEAS) with subjective health. At baseline, DHEAS was measured in participants aged 45-83 randomly selected from the general population. Subjective mental and physical health were assessed using the 12-item Short Form (SF-12) questionnaire at baseline and two follow-ups. In sex-specific...
Luise Charlotte Behr

Short lifespan under dietary cholesterol depletion is associated with gut dysfunction in Drosophila melanogaster females

2 weeks 4 days ago
Dietary restriction may extend lifespan by improving late-life gut health. Because micronutrients mediate the effects of macronutrient ratios on longevity, we examined how cholesterol limitation affects gut health in female Drosophila melanogaster. Low-cholesterol diets increased intestinal permeability and reduced lifespan, however, not all flies lost barrier function before dying. This indicates gut dysfunction is either a marker of ageing, or contributes to death, but predominantly during...
Brooke Zanco