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Cited by 278Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Donanemab: Appropriate use recommendations

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Rabinovici, G.D., Selkoe, D.J., Schindler, S.E., Aisen, P., Apostolova, L.G., Atri, A., Greenberg, S.M., Hendrix, S.B. +4 more·2025·The Journal of Prevention of Alzheimer's Disease
DOI 10.1016/j.tjpad.2025.100150PMC PMC12180672
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Abstract

Donanemab (Kisunla®), an IgG1 monoclonal antibody targeting N-terminal pyroglutamate-modified forms of amyloid-β, is approved in the United States for treatment of early symptomatic Alzheimer's disease (AD). Appropriate Use Recommendations (AUR) were developed to guide the implementation of donanemab in real-world practice, prioritizing safety considerations and opportunity for effectiveness. The AUR were developed by the AD and Related Disorders Therapeutic Workgroup by consensus, integrating available data and expert opinion. Appropriate candidates for donanemab treatment include persons with mild cognitive impairment or mild dementia due to AD (Clinical Stages 3-4, MMSE 20-30) who have biomarker confirmation of AD pathology by PET or CSF. Tau PET is not required for eligibility. Apolipoprotein E (APOE) genotyping should be performed prior to treatment to inform an individual's risk of developing Amyloid-Related Imaging Abnormalities (ARIA). Pre-treatment MRI should be obtained no more than 12 months prior to treatment. Patients with findings of >4 cerebral microbleeds, cortical superficial siderosis or a major vascular contribution to cognitive impairment should be excluded from treatment. The decision to initiate therapy should be grounded in a shared decision-making process that emphasizes the patient's values and goals of care. Donanemab is administered as a monthly intravenous infusion. Surveillance MRIs to evaluate for ARIA should be performed prior to the 2nd, 3rd, 4th and 7th infusions, prior to the 12th dose in higher risk individuals, and at any time ARIA is suspected clinically. Clinicians may consider discontinuing treatment if amyloid clearance is demonstrated by amyloid PET, typically obtained 12-18 months after initiating treatment.

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Authors
Rabinovici, G. D., Selkoe, D. J., Schindler, S. E., Aisen, P., Apostolova, L. G., Atri, A., Greenberg, S. M., Hendrix, S. B., Petersen, R. C., Weiner, M., Salloway, S., & Cummings, J.
Affiliations
  • University of California, San Francisco (US)
  • Brigham and Women's Hospital (US)
  • Washington University in St. Louis (US)
  • University of Southern California (US)
  • Indiana University Indianapolis (US)
  • Harvard University (US)
  • Mayo Clinic (US)
  • Brown University (US)
  • University of Nevada, Las Vegas (US)
Corresponding author
Rabinovici, G.D.
ORCID
Venue
The Journal of Prevention of Alzheimer's Disease
Publisher
Elsevier BV
Published
2025-05
Volume
12
Issue
5
Pages
100150
ISSN
2274-5807 (ISSN-L)
DOI
10.1016/j.tjpad.2025.100150
PMC
PMC12180672
OpenAlex
W4408988700
Cited by
278
References
13
Citations by year
2026: 202 · 2025: 76
FWCI
155.95
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Prevention of Alzheimer s Disease (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
Funders
  • Bristol-Myers Squibb (P20GM109025)
  • Alzheimer's Drug Discovery Foundation (P20GM109025)
  • Eli Lilly and Company (P20GM109025)
  • Biogen (P20GM109025)
  • Alnylam Pharmaceuticals
  • Sunovion
  • Prothena
  • University of Oxford
  • Eisai (P20GM109025)
  • Novo Nordisk
  • H. Lundbeck A/S (P20GM109025)
  • Grifols
  • Genentech (P20GM109025)
  • Allergan
  • Avid Radiopharmaceuticals
  • National Institute on Aging (R25AG083721, P30AG072980, R35AG071476)
  • National Institute of General Medical Sciences (NIA R35AG71476, P20GM109025)
  • National Institute of Neurological Disorders and Stroke (RO1NS139383, R01NS139383)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
donanemab, Alzheimer's disease, amyloid-beta, pyroglutamate amyloid-beta, amyloid PET, APOE genotyping, amyloid-related imaging abnormalities, cerebral microbleeds, mild cognitive impairment, shared decision-making, amyloid clearance, treatment eligibility, treatment discontinuation
MeSH terms
Alzheimer Disease, Humans, Amyloid beta-Peptides, Cognitive Dysfunction, Antibodies, Monoclonal, Humanized

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