Milestone 07 April 2024

Alzheimer's disease

We have entered a new era in Alzheimer’s disease therapy following the FDA approval of two amyloid-β-targeting monoclonal antibodies, the first disease-modifying therapies to enter clinical use. Here, Nature and Nature Reviews Neurology celebrates 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.

This Milestone is editorially independent, produced with financial support from a third party. About this content.

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Developing the ATX(N) classification for use across the Alzheimer disease continuum

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.
- Harald Hampel
- Jeffrey Cummings
- Andrea Vergallo
Perspective8 Jul 2021 Nature Reviews Neurology
Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials

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.
- Willa D. Brenowitz
- Kristine Yaffe
Perspective31 Oct 2022 Nature Reviews Neurology
Gene–environment interactions in Alzheimer disease: the emerging role of epigenetics

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.
- Lucia Migliore
- Fabio Coppedè
Review Article30 Sep 2022 Nature Reviews Neurology
Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility

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.
- Thomas K. Karikari
- Nicholas J. Ashton
- Henrik Zetterberg
Review Article18 May 2022 Nature Reviews Neurology
Early-stage Alzheimer disease: getting trial-ready

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.
- Paul S. Aisen
- Gustavo A. Jimenez-Maggiora
- Rema Raman
Review Article4 Apr 2022 Nature Reviews Neurology
Tau-targeting therapies for Alzheimer disease: current status and future directions

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.
- Erin E. Congdon
- Changyi Ji
- Einar M. Sigurdsson
Review Article24 Oct 2023 Nature Reviews Neurology
A global view of the genetic basis of Alzheimer disease

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.
- Christiane Reitz
- Margaret A. Pericak-Vance
- Richard Mayeux
Review Article6 Apr 2023 Nature Reviews Neurology
New insights into the genetic etiology of Alzheimer’s disease and related dementias

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.
- Céline Bellenguez
- Fahri Küçükali
- Jean-Charles Lambert
ArticleOpen Access4 Apr 2022 Nature Genetics
A computational model of neurodegeneration in Alzheimer’s disease

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.
- D. Jones
- V. Lowe
- C. Jack
ArticleOpen Access28 Mar 2022 Nature Communications
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics

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.
- Eric Karran
- Bart De Strooper
Perspective17 Feb 2022 Nature Reviews Drug Discovery

Alzheimer's disease

More from Nature Portfolio

Developing the ATX(N) classification for use across the Alzheimer disease continuum

Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials

Gene–environment interactions in Alzheimer disease: the emerging role of epigenetics

Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility

Early-stage Alzheimer disease: getting trial-ready

Tau-targeting therapies for Alzheimer disease: current status and future directions

A global view of the genetic basis of Alzheimer disease

New insights into the genetic etiology of Alzheimer’s disease and related dementias

A computational model of neurodegeneration in Alzheimer’s disease

The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics

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