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Inside the evidence revolution — how decision-making became data driven
Cosmic-ray detection heralds era of mega-observatories for neutrinos
Connecting fragmented aging research through the European Federation for Aging Research
The memory dealer of Old Jeddah
Hit a glitch in your research? Some ‘night science’ thinking could move it forward
Brain tissue near tumours is loaded with plastic
From bats at dusk to asteroid quests: Books in brief
Author Correction: A µ-opioid receptor superagonist analgesic with minimal adverse effects
Author Correction: Commensal yeast promotes <i>Salmonella</i> Typhimurium virulence
Closure of China’s influential journal ranking leaves academics reeling — what will take its place?
After pulling vaccine study, Bhattacharya criticizes long-running CDC publication
Agency’s temporary director says Morbidity and Mortality Weekly Report needs external reviewers
Can Starship succeed where the space shuttle struggled?
As SpaceX readies its latest megarocket, engineer Stephen Whitmore explains why atmospheric reentry pushes materials to their limits
UK Biobank faces questions about data security after latest breach
Experts say the lapse highlights that even new measures to control access did not safeguard deidentified patient information
Abrupt change to European funder’s rules leaves researchers shut out
Flood of proposals to European Research Council—perhaps unleashed by AI—means unsuccessful applicants must wait longer to reapply
Organelle interactome disruption: The systemic pathological mechanisms and therapeutic prospects of mitochondria-lysosome-ER crosstalk in Alzheimer's disease
The traditional pathological framework of Alzheimer's disease (AD) primarily focuses on the accumulation of β-amyloid (Aβ) and tau proteins. However, therapeutic strategies targeting these molecules have repeatedly encountered setbacks in clinical translation. Recent studies have progressively revealed that the dynamic interaction network among intracellular organelles plays a central role in the pathogenesis of AD. This systematic review examines the independent dysfunctions of three key...
TNMD BRICHOS domain attenuates tau pathology and memory deficits in a mouse model of tauopathy
The aberrant aggregation of tau leads to loss of its physiological functions and gain of toxic functions, and plays a crucial role in the pathogenesis of tauopathies including Alzheimer's disease (AD). Targeting tau aggregation is considered a promising strategy for treating tauopathies. The BRICHOS family consists of a variety of proteins containing the BRICHOS domain. Certain endogenous BRICHOS domains may inhibit the pathological aggregation of disease-associated proteins. However, the...
Type I interferon drives T cell responses to amyloid beta in the central nervous system
Amyloid beta (Aβ) plaque deposition in the central nervous system (CNS) is a hallmark of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), triggering robust innate immune responses. However, the role of the adaptive immune system remains less well understood. Here we show the immune microenvironment dynamics in APP23 transgenic (APP23-tg) mice modelling CNS amyloid pathology, using single-cell transcriptomics. We observed a marked increase in T-cell populations during late disease...
Early dopamine disruption in the entorhinal cortex of a knock-in model of Alzheimer's disease
The entorhinal cortex is a critical brain area for memory formation, while also the region exhibiting the earliest histological and functional alterations in Alzheimer's disease (AD). The entorhinal cortex therefore has been long hypothesized as one of the originating brain areas of AD pathophysiology, although circuit mechanisms causing its selective vulnerability remain poorly understood. Here we show that dopamine neurons projecting their axons to the lateral entorhinal cortex (LEC), critical...
AAV-based gene therapy with modified HEXB confers lasting therapeutic benefits in GM2 gangliosidosis models
GM2 gangliosidoses, including Tay-Sachs (TSD) and Sandhoff (SD) diseases, are lysosomal storage disorders with neurological manifestations caused by the excessive accumulation of GM2 ganglioside due to the deficiency of the β-hexosaminidase A (HexA). Although gene therapy approaches are underway, concerns regarding efficacy and safety remain. Here, we evaluate a tyrosine-mutant adeno-associated virus serotype 9 (AAV9/3) vector encoding modified HEXB (modHEXB) wherein nine amino acid residues are...
The long-lived immune system of centenarians
Centenarians - individuals aged 100 years or older - constitute a biologically distinct human population that achieves exceptional longevity while frequently retaining functional independence and avoiding major age-related diseases or postponing their onset. Despite their advanced age, many centenarians show relatively preserved immune function and resistance to conditions linked to immunosenescence and chronic low-grade inflammation (inflammageing). These features are especially pronounced in...