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Jack CR Jr, et al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024;20:5143-5169. PMID 38934362

One-paragraph summary

An Alzheimer's Association workgroup updated the 2018 NIA-AA research framework, extending the principle of defining disease biologically rather than syndromically from research into diagnosis and staging. The document defines Alzheimer's disease as a biological process that begins with the appearance of Alzheimer's neuropathologic change while people are asymptomatic. Early-changing Core 1 biomarkers — amyloid PET, approved CSF biomarkers, and accurate plasma biomarkers, especially phosphorylated tau 217 — map onto either the amyloid-β or the AD tauopathy pathway but reflect the presence of ADNPC more generally; an abnormal Core 1 result is stated to be sufficient to establish a diagnosis of AD and to inform clinical decision-making across the continuum. Later-changing Core 2 biomarkers (biofluid and tau PET) provide prognostic information and, when abnormal, increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme accommodates the fact that common copathologies, cognitive reserve and resistance modify the relationship between clinical and biological stage (PMID 38934362).

Key findings

  • AD is defined as beginning with asymptomatic neuropathologic change; symptoms are a later consequence.
  • Core 1 biomarker abnormality is sufficient for diagnosis, removing the requirement for a clinical syndrome.
  • Core 2 biomarkers are prognostic, not diagnostic.
  • Integrated biological + clinical staging explicitly accommodates copathology and reserve.
  • The document declines to be a workflow guideline; it offers general principles rather than step-by-step protocols or treatment algorithms.

Limitations

  • No empirical validation accompanies the diagnostic threshold: the criteria do not establish what proportion of Core 1-positive asymptomatic people will become symptomatic, or over what horizon.
  • Available progression data cut both ways: 5-year progression to symptomatic AD in cognitively normal people was 11% at NIA-AA stage 1 (Vos 2013, PMID 24012374) and 17% with amyloid alone, versus 57% when tau PET was also positive (Moscoso 2025, PMID 40522652).
  • Criteria choice materially changes measured prevalence: in the same 259 unimpaired 70-year-olds, "preclinical AD" prevalence ranged from 9.7% to 22.8% depending on the scheme applied (Kern 2018, PMID 29653987).
  • Consequences of diagnosis for insurance, employment and legal capacity are not addressed.

Why it matters

This is the document that made "having Alzheimer's disease" a biomarker fact rather than a clinical one, and it is the proximate cause of the field's sharpest live disagreement: the International Working Group responded that most biomarker-positive cognitively normal individuals will not become symptomatic on a proximate timeline and should be described as at risk for AD, not as having it (Dubois 2024, PMID 39483064). Because plasma p-tau217 can now be measured cheaply and accurately (Therriault 2025, PMID 40818474), the criteria's practical reach is far larger than that of any previous research framework — every population these assays touch is a population this definition classifies.

Cited by wiki pages

  • diagnostic criteria and the biological definition
  • clinical presentation and staging
  • fluid biomarkers
  • guidelines
  • overview