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Preclinical Alzheimer's disease (AD) is associated with distressing neuropsychiatric symptoms (NPSs) that may accelerate progression toward dementia. Existing approaches probe the symptom-level domain-general or domain-specific neural correlates of NPSs. However, the field lacks process-oriented models of symptom emergence for targeted treatment. We propose one pathway for symptom emergence involving the disruption of emotion regulation (ER) systems by early AD pathology. AD pathology in the...

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by β-amyloid (Aβ) deposition, tau hyperphosphorylation, neuroinflammation, and cholinergic dysfunction. Currently, no disease-modifying drugs are available, and existing symptomatic treatments offer limited efficacy while posing safety concerns, highlighting the urgent need for multi‑target therapeutic strategies. The natural β‑carboline alkaloid harmine has attracted considerable attention due to its favorable...

Major depressive disorder (MDD) is associated with widespread alterations in functional brain networks across the lifespan. However, heterogeneity in atypical brain development among patients with MDD remains largely uncharacterized. Using a multisite resting-state functional MRI dataset consisting of 1,105 MDD patients and 1,065 healthy controls, we constructed a harmonized multicenter brain age prediction model based on individualized functional topography and identified two patient subgroups...

Phenotypic heterogeneity is prevalent during aging, yet its underlying molecular drivers remain poorly understood. In budding yeast, two distinct aging trajectories, characterized by either ribosomal DNA (rDNA) instability or mitochondrial decline, have been proposed to be mutually exclusive. Here, we systematically dissect the heterogeneity among aging yeast cells by combining single-cell transcriptomics with longitudinal fluorescence microscopy. Our data reveal distinct transcriptional...

The EAT-Lancet diet (ELD) and plant-based diets (PBDs) are recommended for their potential health and environmental benefits, but comparative analyses of these dietary patterns in relation to mortality risk remain limited. This study aimed to evaluate the associations of ELD and PBDs with mortality and life expectancy in two nationwide cohorts. Participants from the UK Biobank and the US National Health and Nutrition Examination Survey (NHANES) (2003-2018) were included. Dietary intake was...

Sex-specific trajectories of vascular aging may influence stroke recovery, yet their impact on access to reperfusion and long-term outcomes remains uncertain. We analysed 3760 consecutive patients with angiography-confirmed cerebral vessel occlusion transferred for endovascular therapy (EVT) between 2015 and 2022. Women accounted for 45.1% of patients and were significantly older (median 77 vs. 70 years) with greater baseline stroke severity (NIHSS 14 vs. 12). Access to acute stroke care was...

Extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated Tau are the two main pathological hallmarks of Alzheimer's disease (AD). Although the co-occurrence and synergistic effects of Aβ and Tau are well established, the mechanisms underlying their interplay in a biomolecular condensate environment remain unclear. Here we show that Aβ40 does not undergo liquid-liquid phase separation (LLPS) but significantly enhances Tau phase...

Parkinson's disease (PD) and related familial Parkinsonism are defined by motor dysfunction, but the specific upstream molecular causes of these clinical symptoms can vary widely. We hypothesize that these causes converge onto a limited number of core cellular pathways. To investigate this, we created a collection of 24 genetically well-controlled Drosophila models of familial forms of PD and related mono-genic forms of Parkinsonism. Using unbiased behavioral screening and machine learning we...

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Cellular senescence, originally described as a finite proliferative arrest in cultured somatic cells, has since been recognized as a central mechanism underlying aging and the development of age-associated disorders. The progressive accumulation of senescent cells (SnCs) promotes chronic inflammation through the senescence-associated secretory phenotype (SASP) and circumvents immune-mediated clearance by upregulating pro-survival and immune checkpoint pathways. Early "first-generation"...

A growing body of evidence supports the role of nutrient sensing and metabolism pathways in regulating ageing rate and healthspan, but the diversity of human lifestyles challenges our ability to identify the mechanisms of this age acceleration. Here, we examine how the transition of wild King penguins to zoo husbandry can closely mimic the shift to a Western lifestyle in humans, and shed light on conserved epigenetic changes in responses to sedentary conditions. We show that, just like modern...

Cellular morphology is tightly linked to function, but how subcellular transcript localization contributes remains unclear. Using microglia, the brain's resident macrophages, as a model, we combined multiplexed error-robust fluorescence in situ hybridization with immunohistochemistry to map how morphology and subcellular mRNA localization interact with function in young and aged mouse brains. We show that mRNA spatial organization varies across microglial states and defines distinct localization...

The postmenopausal decrease in estrogen production contributes to a significant increase in the risk of age-related diseases. There is an identified gap in the field regarding the effectiveness of targeted interventions for specific groups of women at increased risk, and whether these interventions can support successful aging and reduce mortality. Data regarding 2239 Caucasian female participants of the PolSenior study aged 65 and over were analyzed. Based on strict criteria, participants were...

CONCLUSIONS: This work establishes a valuable transcriptomic resource for glial GABA-associated ASH neuronal aging and identifies candidate pathways, offering critical molecular insights to dissect age-related neurodegeneration mechanisms and inform potential therapeutic targets.

A physicist and professional dancer takes home the grand prize, and Science awards its first trophy for an AI-assisted dance concept