Monoclonal antibodies against beta-amyloid protein (lecanemab and donanemab) should not be used in the treatment of Alzheimer's disease
Open accessAbstract
Two antiamyloid monoclonal antibodies (mAbs), lecanemab and donanemab, were recently launched for treatment of Alzheimer's disease (AD). These mAbs remove amyloid protein from the brain and cause statistically significant improvement in cognitive/functional tests, meaning a change in evolution of AD. This is important to reinforce the amyloid cascade hypothesis and to further concentrate studies on the pathways from the deposition of the beta-amyloid protein to synaptic loss and neuronal death. However, it is necessary to evaluate whether the results are clinically important. Analysis of the clinical trials showed that the statistically significant differences over placebo did not reach the minimum clinically important difference that would be meaningful for patients, caregivers and clinicians. Besides, the incidence of adverse events is high and potentially severe. Although there are reasons to celebrate this first step towards disease-modifying therapies for AD, lecanemab and donanemab should not be used to treat AD in clinical pratice.
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Monoclonal antibodies targeting Aβ, including lecanemab and donanemab, demonstrate modest disease-modifying potential.
“More recently, monoclonal antibodies targeting amyloid-β (Aβ), including lecanemab and donanemab, have marked a milestone in the field by demonstrating modest disease-modifying potential [4, 5].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [5]
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Cites
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
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Donanemab in Early Alzheimer’s Disease
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Hein, Z. M., Karikalan, B., Gopalakrishna, P. K., Dhevi, K., Alkatiri, A., Hussan, F., Mohd Moklas, M. A., Jagadeesan, S., Che Ramli, M. D., Che Mohd Nassir, C. M. N., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05602-0 · Cited by 43 · see citing works
- Authors
- Nitrini, R., & Studart-Neto, A.
- Affiliations
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, Grupo de Neurologia Cognitiva e do Comportamento, São Paulo SP, Brazil.
- Venue
- Arquivos de Neuro-Psiquiatria
- Publisher
- Georg Thieme Verlag KG
- Published
- 2025-05
- Volume
- 83
- Issue
- 05
- Pages
- 001-005
- ISSN
- 0004-282X (ISSN-L)
- 1678-4227
- PMC
- PMC12064297
- OpenAlex
- W4410221453
- Cited by
- 6
- References
- 3
- Citations by year
- 2026: 3 · 2025: 3
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Arquivos de Neuro-Psiquiatria (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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
- Alzheimer's disease, lecanemab, donanemab, anti-amyloid monoclonal antibodies, amyloid-beta, amyloid hypothesis, disease-modifying therapy, minimal clinically important difference, adverse events, clinical trial results, synaptic loss, neuronal cell death
- MeSH terms
- Alzheimer Disease, Antibodies, Monoclonal, Clinical Trials as Topic, Humans, Amyloid beta-Peptides, Antibodies, Monoclonal, Humanized
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