Basic Science & Clinical Practice

New Criteria for Diagnosing and Staging Alzheimer's Disease: What They Mean for APOE ε4 Carriers

A physician's guide to the 2024 Alzheimer's Association Workgroup criteria, the competing International Working Group framework, and what real-world validation data mean for genetically at-risk individuals.

In 2024, the Alzheimer's Association (AA) Workgroup published the most consequential revision to Alzheimer's disease (AD) diagnostic criteria in over a decade. The update did not go unchallenged — a rival international consensus body issued a formal dissent just months later — and the first large, independent validation studies of the new staging system have since revealed a level of clinical-biological discordance that carries direct implications for anyone carrying the APOE ε4 allele. This article summarizes what changed, what remains contested, and what it means for ε4 carriers weighing biomarker testing.

From Syndrome to Biology

The National Institute on Aging and Alzheimer's Association (NIA-AA) convened workgroups in 2011 and 2018 to move AD diagnosis toward a biomarker-based framework. The 2018 "AT(N)" research framework required both amyloid positivity (A+) and tau positivity (T+) to establish a biological definition of AD, and it was explicitly limited to research use.1

The 2024 revision, authored by the AA Workgroup alone (the NIA now serves only in an advisory role), extends this biological framework into clinical practice. Its central premise mirrors an approach long standard in oncology: define the disease by its underlying pathology, not by the symptoms it eventually produces. Alzheimer's disease is now formally defined as beginning with the appearance of AD neuropathologic change (ADNPC) years to decades before any symptoms emerge.1