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SK channel upregulation and sex-specific mechanisms drive spinal motoneuron reduced excitability with age

12 hours 20 minutes ago
INTRODUCTION: Mechanisms underlying age-related weakness are not fully understood, with neuronal mechanisms recently gaining attention. Despite studies on excitatory and inhibitory inputs, conflicting findings on α-motoneuron intrinsic excitability and PIC changes highlight a major gap in explaining age-related strength decline.
Ibrahim Abdul Halim

Changes in the brain [NAD(+)]/[NADH] and [NADPH]/[NADP(+)] with aging and anti-aging dietary restriction

12 hours 20 minutes ago
Changes in brain [NADPH]/[NADP^(+)] and [NAD^(+)]/[NADH] may contribute to aging. Anti-aging dietary restriction (DR) and intermittent fasting (IF) alter redox states that may contribute to their longevity effects. Pyruvate/lactate and acetoacetate/beta-hydroxybutyrate are indicators of the cytoplasmic and mitochondrial [NAD^(+)]/[NADH], respectively, while the malate/pyruvate and isocitrate/alpha-ketoglutarate are indicators of the cytoplasmic [NADPH]/[NADP^(+)]. Using these metabolite-pair...
Leah E Jamerson

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

1 day 12 hours 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

1 day 12 hours 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

1 day 12 hours 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

1 day 12 hours 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

1 day 12 hours 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?

1 day 12 hours 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

1 day 12 hours 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