Alzheimer's disease articles from across Nature Portfolio

Structural studies support the idea that fibrillized tau protein, a feature of neurodegenerative disorders, acts as a prion-like template to induce misfolding in healthy tau.

Not all selective markers of seeding-competent Tau are known. Here, the authors identify pS65-Ub-associated tau linked to pathological Tau spreading and elevated in Alzheimer’s disease. Removal of pS65-Ub reduces tau seeding activity.

A large-scale study identified 107 brain DNA methylation sites linked to Alzheimer’s pathology, with 38 replicated independently. DNA methylation partially mediated the association between APOE genotype and Alzheimer’s diagnosis.

This study identifies common structural variants contributing to Alzheimer’s disease heritability. An expanded promoter CCG repeat increases FAM193B expression and disease risk, linking its expression to DNA damage and cell death pathways in neurons.

Chen and colleagues use a heterozygous mouse model carrying human APOE2 and APOE4 alleles to show that APOE2 attenuates APOE4- associated effects on brain amyloid pathology and related cellular and molecular changes.

Hou et al. show a drug target compendium supported by human genetic and real-world patient data for Alzheimer’s disease and validate epoxide hydrolase 2 as a causal Alzheimer’s disease target using CRISPR interference and gene editing experiments in human models.

Structural studies support the idea that fibrillized tau protein, a feature of neurodegenerative disorders, acts as a prion-like template to induce misfolding in healthy tau.

The atlas of gene expression in the prefrontal cortex was created using samples from almost 1,500 donors of all ages — from infants to centenarians.

Multiple modifiable risk factors for dementia commonly co-occur in a large proportion of the population, challenging the distinction between individuals at high risk and the wider population. Dementia prevention should therefore move beyond binary eligibility towards a combination of population-wide prevention and intensive interventions that reflect the continuum of risk.

The trait could explain why symptoms vary in severity between people with similar brain pathology.

Alzheimer’s disease (AD) remains a major unmet medical challenge, highlighting the need for improved experimental models. The second Unconventional Animal Models of Alzheimer’s Disease and Aging (UAMAA 2026) conference brought together ~150 interdisciplinary researchers to discuss advances across 19 animal models of AD and aging. Six major themes emerged: naturally occurring AD-like pathology, neuroinflammation, population heterogeneity, development of genomic and molecular resources, companion dogs as translational models and the promise of laboratory-amenable species such as the Chilean degu and common marmoset. These discussions highlighted the growing value of cross-species approaches for advancing translational AD research.