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Immunotherapy with B28, an antibody to Aβ oligomers, potently decreases amyloid plaques, microgliosis, and memory decline in APP knock-in mice

18 hours 26 minutes ago
Immunotherapy against amyloid β-protein (Aβ) for Alzheimer's disease (AD) has been widely approved. Breakthrough disease-modifying treatments such as lecanemab and donanemab are often followed by drugs with improved efficacy. By immunizing Trianni mice with aggregated synthetic Aβ, we obtained B28, a fully human antibody specifically selected for its neutralization of tau neuritic dystrophy induced by AD brain-derived oligomers. In a blinded trial in mutant human APP^(NL-G-F) knock-in mice,...
Ting Yang

A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt-Jakob disease prions

18 hours 26 minutes ago
Prion diseases represent a unique biological paradigm with mechanistic parallels to other neurodegenerative conditions like Alzheimer's and Parkinson's diseases. However, the study of human prion pathobiology and the development of effective therapeutics has been severely constrained by the inability to propagate human prions in dividing cells-forcing reliance on costly and slow animal bioassays. Here, we report the generation of EKV cells-a humanized cell model which supports the robust,...
Akin Nihat

Tau protein as a regulator of mitochondrial function and dynamics

18 hours 26 minutes ago
Mitochondrial damage is a shared hallmark of brain aging and neurodegeneration. While pathological Tau mutations disrupt mitochondrial dynamics and function, the physiological role of wild-type (WT) Tau in the maintenance of mitochondrial homeostasis remains poorly understood. Here, using Caenorhabditis elegans and mice lacking PTL-1, the nematode Tau-like homolog, and Tau respectively, we demonstrate that Tau deficiency promotes a shift toward a pro-fusion mitochondrial state associated with...
Eleni Tsakiri

The influence of aging on graded peripheral venous return and complex blood flow features through human veins

18 hours 26 minutes ago
Aging is associated with reduced venous compliance and altered muscle pump function, though how these features impact venous return during volume-stressed conditions remains poorly characterized. We examined lower-limb venous flow dynamics and muscle pump efficiency between healthy younger (YA) and older adults (OA) under two volume-stressed conditions. Fourteen YA (7F, 26 ± 4 years) and fourteen OA (9F, 76 ± 6 years) underwent assessments at head-down tilt (HDT, -3°) and head-up tilt (HUT, +...
Jeremy N Cohen

A Gut-Centric View of Ageing: A Pilot Analysis Mapping Age-Associated Immune and Molecular Alterations in Colonic Mucosa Using Spatial Proteomics

18 hours 26 minutes ago
Investigating age-associated changes in intestine and understanding immune-related intestinal dysfunctions is essential for promoting healthy ageing. Mucosal surfaces represent a distinct immune compartment enriched with specialised lymphocytes that interact dynamically with the epithelial layer. In this study, we present novel spatially resolved insights into the cellular and molecular alterations in the ageing murine gut mucosa. Our findings reveal a complex network of interdependent...
Jack Sullivan

Clonal Analyses Reveal the Impact of Hematopoietic Stem and Progenitor Cell Aging on T Cell Development

18 hours 26 minutes ago
T cell output from the thymus falls throughout life and is associated with profound remodeling of the thymic stroma. To what extent the decline in T cell output is caused by aging of the hematopoietic stem and progenitor cells (HSPCs) has been difficult to define because of HSPC heterogeneity, the multi-stage process of HSPC migration, and the cross-talk between hematopoietic and stromal elements of the thymus. To address the contribution of HSPC aging on T cell development, we interrogated T...
Julia Gensheimer

High-saturated-fat diet drives female-biased neurodegeneration in <em>Drosophila</em> via oxidative stress and impaired autophagic flux

18 hours 26 minutes ago
CONCLUSION: These findings identify oxidative stress and disrupted autophagy as key mediators of saturated-fat-induced neuronal decline and highlight a sex-specific vulnerability to dietary fat composition. This work establishes Drosophila as a powerful model for dissecting nutritional drivers of neural aging and suggests that metabolic stress pathways represent critical early targets in diet-associated neurodegeneration.
A M Taylor