Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
We have entered a new era in Alzheimer’s disease therapy following the FDA approval of amyloid-β-targeting monoclonal antibodies, the first disease-modifying therapies to enter clinical use. Here, Nature and Nature Reviews Neurology celebrate the milestones in the Alzheimer’s disease research field that have moved us closer to early and effective intervention.
This Milestone will launch in full in Summer 2024. A collection of related articles from across the Nature Portfolio is available to access now.
The AT(N) system is a classification scheme based on biomarkers that reflect the core pathophysiological features of Alzheimer disease. This Perspective outlines the conceptual framework and clinical importance of the AT(N) system and considers its potential expansion to incorporate biomarkers for additional pathophysiological mechanisms.
In this Perspective, the authors discuss the importance of performing well-designed observational studies on Alzheimer disease. They highlight novel approaches to enhance causal inference and discuss ways in which observational data can provide a bridge between preclinical findings and clinical trials.
Most cases of Alzheimer disease (AD) have a complex aetiology, probably involving multiple genetic and environmental factors. In this Review, the authors discuss how various environmental AD risk factors could induce epigenetic modifications of key AD-associated genes and pathways.
Recent technological advances have enabled the detection of specific forms of phosphorylated tau in blood. Here, the authors summarize the performance of blood phosphorylated tau biomarkers in the context of Alzheimer disease and highlight related ethical, analytical and clinical challenges.
Consensus is growing that intervention in the very early stages of Alzheimer disease is necessary for disease modification. Here, the authors discuss the challenges of recruiting asymptomatic or mildly symptomatic participants for clinical trials, focusing on ‘trial-ready’ cohorts as a potential solution.
The limited success of amyloid-β-targeting therapies for Alzheimer disease has led to a shift in focus towards the tau protein. This Review provides an update on the initial trials of tau-targeting therapies, focusing particularly on immunotherapies, and considers future directions for these therapies.
In the field of Alzheimer disease genetics, a lack of ancestral diversity in study cohorts is limiting progress. Here, the authors summarize our current knowledge of Alzheimer disease genetics in populations across the world and highlight efforts to increase cohort diversity.
Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.
Low-dimensional representations of functional brain anatomy relevant for dementia syndromes may exist. Here the authors propose a computational model of mental functions to catalogue this anatomy in Alzheimer’s and related dementias.
Many drugs that target amyloid-β in Alzheimer disease have failed in clinical trials. Karran and De Strooper analyse clinical trial data for these drugs in the light of drug properties that could affect their clinical performance. They propose that amyloid plaque would need to be reduced to a low level to reveal significant clinical benefit and that there will be a lag between the removal of amyloid and the potential to observe such a benefit.