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Science, Volume 390, Issue 6768, Page 34-34, October 2025.

Science, Volume 390, Issue 6768, Page 35-35, October 2025.

Coalition that runs premier climate modeling center faces rising costs and budget uncertainty

Researchers expose flaws in safeguards intended to block rogue actors from making bioweapons

Tubes in mouse and human brains may also influence spread of brain disease

Recent clinical successes, and profits, have prompted a rush among pharma companies to try new isotopes and targeting strategies

25-year plan will tap brain-mapping prowess in two dozen countries to visualize the organ in unprecedented detail

300,000-year-old genes are oldest ever recovered from open-air site

Integrating single-cell RNA sequencing with Genome-Wide Association Studies (GWAS) can uncover cell types involved in complex traits and disease. However, current methods often lack scalability, interpretability, and robustness. We present seismic, a framework that computes a novel specificity score capturing both expression magnitude and consistency across cell types and introduces influential gene analysis, an approach to identify genes driving each cell type-trait association. Across over...

The accumulation of intracellular aggregates of Tau protein is one main hallmark of Alzheimer's disease (AD) and is the consequence of Tau conformational changes, increased phosphorylation, and self-association to form fibrillar aggregates. This pathological process prevents the physiological interaction of Tau with microtubules to the detriment of the structural integrity of neurons. In healthy cells, aberrant protein misfolding and aggregation are counteracted by chaperone proteins whose...

No abstract

On the basis of extensive mechanistic research over three decades, Parkinson disease (PD) and related synucleinopathies have been proposed to be combined proteinopathies and lipidopathies. Evidence strongly supports a physiological and pathogenic interplay between the disease-associated protein α-synuclein and lipids, with a demonstrable role for lipids in modulating PD phenotypes in the brain. Here, we refine this hypothesis by proposing PD to be a disease specifically involving metabolic...

Parkinson's disease (PD) is a neurodegenerative condition characterized by the presence of intraneuronal aggregates containing fibrillar ɑ-synuclein known as Lewy bodies. These large end-stage species are formed by smaller soluble protein nanoscale assemblies, often termed oligomers, which are proposed as early drivers of pathogenesis. Until now, this hypothesis has remained controversial, at least in part because it has not been possible to directly visualize nanoscale assemblies in human brain...

Extracellular Tau determines the progression of Alzheimer's disease, yet therapeutic strategies targeting it are hindered by poor brain delivery and limited clearance. Here we developed a Tau-clearing cell therapy based on monocytes functionalized with a high-affinity Tau-specific aptamer. The aptamer was covalently conjugated to the surface of monocytes (derived from bone marrow leucocytes and cultured under monocyte-inducing conditions) via bioorthogonal chemistry without affecting their...

The locus coeruleus (LC) is a brainstem nucleus best known for being the primary site of noradrenaline production for the forebrain and is involved in the modulation and optimization of behavioral performance. The LC has many targets throughout the cortex, and ascending projections from the LC join the central tegmental tract (CTT), a well-defined white matter brainstem tract in the pons that terminates in the thalamus. Evidence indicates that the LC is one of the first brain regions to show...

Life expectancy has been increasing over the last decades, which is not matched by an increase in healthspan. Besides genetic composition, environmental and nutritional factors influence both health- and lifespan. Diet is thought to be a major factor for healthy ageing. Here, we show that dietary RNA species improve proteostasis in C. elegans. Inherent bacterial-derived double stranded RNA reduces protein aggregation in a C. elegans muscle proteostasis model. This beneficial effect depends on...

We aimed to determine reference values for handgrip strength in Europe. Data from the Survey of Health, Ageing and Retirement in Europe were used, involving adults aged 50 + years. Reference values were expressed as weighted percentiles for absolute (kg) and relative (kg/m²) handgrip strength. For women, the highest absolute handgrip strength was observed among the 50-54-year-olds (standing: 5th percentile [P5] = 19 kg; 50th percentile [P50] = 29 kg; 95th percentile [P95] = 39 kg, sitting: P5 =...

No abstract

Meningeal lymphatic vessels (MLVs) have been identified to associate with various neurological diseases, such as traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and brain tumors. Damage to MLVs can exacerbate the pathological progression of these diseases and significantly impede therapeutic efficacy. Therefore, targeted repair of the damaged MLVs has emerged as an innovative strategy for treating these central nervous system (CNS) diseases. In...

The conversion of proteins into insoluble fibrillar aggregates known as amyloid occurs in a wide variety of diseases, e.g., Alzheimer's disease, amyotrophic lateral sclerosis, systemic transthyretin amyloidosis, and multisystem atrophy. There are more than 60 disease-associated amyloid-forming proteins, and amyloid formation can occur sporadically or can be induced or accelerated by genetic mutations. This Review discusses structural mechanisms by which genetic changes promote amyloid formation...