Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup
Open accessAbstract
The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step‐by‐step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. Highlights: We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later‐changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.
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Alzheimer's disease is characterized by two core biomarkers: amyloid beta plaques and tau neurofibrillary tangles.
“Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by two core biomarkers: amyloid beta (Aβ) plaques and tau neurofibrillary tangles.”
From Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial–oligodendrocyte responses (2026) · cites this paper as [2]
The Biomarker Categorization section identifies Aβ and tau as core biomarker categories, and the Highlights describe AD neuropathologic change as including neuritic plaques and tangles. But the paper distinguishes those pathologic deposits from the biomarker tests that detect or reflect them; it does not call plaques and tangles themselves the two core biomarkers. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe updated diagnostic framework incorporating fluid and imaging biomarkers enables more precise staging and individualized treatment plans.
“The updated diagnostic framework, incorporating fluid and imaging biomarkers, enables more precise staging and individualized treatment plans.”
From A 2025 update on treatment strategies for the Alzheimer’s disease spectrum (2025) · cites this paper as [11]
The six stages of Alzheimer's disease along its continuum are defined by the latest research published in 2024.
“This section describes the six stages of AD along its continuum, as defined by the latest research published in 2024 (Table 2).11,12”
From A 2025 update on treatment strategies for the Alzheimer’s disease spectrum (2025) · cites this paper as [11]
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- Authors
- Jack, C. R., Andrews, J. S., Beach, T. G., Buracchio, T., Dunn, B., Graf, A., Hansson, O., Ho, C., Jagust, W., McDade, E., Molinuevo, J. L., Okonkwo, O. C., Pani, L., Rafii, M. S., Scheltens, P., Siemers, E., Snyder, H. M., Sperling, R., Teunissen, C. E., & Carrillo, M. C.
- Affiliations
- Mayo Clinic (US)
- Global Evidence & Outcomes Takeda Pharmaceuticals Company Limited Cambridge Massachusetts USA
- Banner Sun Health Research Institute (US)
- United States Food and Drug Administration (US)
- Michael J. Fox Foundation (US)
- Novartis (Switzerland) (CH)
- Lund University (SE)
- Denali Therapeutics (United States) (US)
- University of California, Berkeley (US)
- Washington University in St. Louis (US)
- Department of Global Clinical Development H. Lundbeck A/S Experimental Medicine Copenhagen Denmark
- University of Wisconsin–Madison (US)
- University of Miami (US)
- University of Southern California (US)
- Amsterdam University Medical Centers (NL)
- Acumen Pharmaceuticals (United States) (US)
- Alzheimer's Association (US)
- Brigham and Women's Hospital (US)
- Medical & Scientific Relations Division Alzheimer's Association Chicago Illinois USA
- Corresponding author
- Jack, Clifford R.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2024-06-27
- Volume
- 20
- Issue
- 8
- Pages
- 5143-5169
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC11350039
- OpenAlex
- W4400089962
- Cited by
- 2,803
- References
- 57
- Citations by year
- 2026: 1361 · 2025: 1233 · 2024: 208
- FWCI
- 823.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- GHR Foundation
- Alzheimer's Association
- Michael J. Fox Foundation for Parkinson's Research
- Biogen
- Eisai
- Fujirebio Europe
- GE Healthcare
- Roche
- National Institute on Aging
- BrightFocus Foundation
- Novo Nordisk
- UCB
- National Multiple Sclerosis Society
- Alzheimer Nederland
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, diagnostic criteria
- MeSH terms
- Alzheimer Disease, Brain, Humans, United States, Biomarkers, tau Proteins, Disease Progression, National Institute on Aging (U.S.)
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