Aducanumab for the treatment of Alzheimer's disease
Abstract
Alzheimer's disease (AD) is the most frequent neurodegenerative condition, the most common cause of dementia, and a leading cause of disability and death globally. Mounting evidence supported accumulation of amyloid β (Aβ) as the primary cause of AD pathology and sprouted a number of candidate treatments engaging Aβ from its production to its clearance, yet no amyloid-based drug candidate had been proven effective. Alternative pathomechanisms have been proposed, but still current treatments are limited to symptomatic therapy. Aducanumab (BIIB-037) is a fully human monoclonal IgG1 antibody that selectively binds aggregated forms of Aβ, inhibits its template activity and promotes clearance of Aβ deposits. Three early terminated trials in humans are available. Overall, conflicting results exist over measures of clinical efficacy, despite an objective decrease in Aβ burden. Amyloid-related imaging abnormalities emerge as the most significant treatment-related adverse event. Here, we provide a comprehensive review of the available evidence on aducanumab, a drug that recently received a debated accelerated approval for the treatment of mild AD by the U.S. Food and Drug Administration (FDA).
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Third-generation human immunoglobulin monoclonal antibodies aducanumab, donanemab, and lecanemab, directed against insoluble, modified, N-terminal truncated amyloid-beta and targeting plaque clearance, seem to benefit mild cognitive impairment or mild Alzheimer's disease dementia patients.
“The third generation of human immunoglobulin monoclonal antibody (hmAB; aducanumab, donanemab, and lecanemab) directed against insoluble, modified, N-terminal truncated form of Aβ, targeting Aβ plaque clearance, seems to benefit MCI or AD with mild dementia patients [34, 37].”
From Current therapeutics for Alzheimer’s disease and clinical trials (2024) · cites this paper as [37]
Most combination therapy trials failed to meet their specific cognitive endpoints.
“However, most of these trials failed to meet each trial’s specific cognitive endpoints, for example, clinical trials of Aβ clearance agent Rosiglitazone as an add-on therapy for patients with AD on donepezil or other AChEIs [37].”
From Current therapeutics for Alzheimer’s disease and clinical trials (2024) · cites this paper as [37]
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“6% of patients on high dose aducanumab in the pivotal trials (5).”
Aducanumab: Appropriate Use Recommendations Update
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“These include acetylcholinesterase inhibitors (tacrine, done-pezil, galantamine, and carbalatine) [9], the N-methyl-D-aspartate (NMDA) receptor antagonist memantine, and aducanumab, which targets Aβ [10].”
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“Until now, the U.S. Food and Drug Administration has only certified six drugs for the treatment of AD; however, most drugs can only relieve symptoms without slowing the progression of the disease (Tagliapietra 2022).”
Current therapeutics for Alzheimer’s disease and clinical trials
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“inhibitory activity against class II HDACs (4, 5, 6, 7, 9), but with weaker class I HDAC inhibition compared to SAHA.”
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“More recently, Aducanumab became the first FDA‐approved drug with the potential to modify disease pathology [2, 68].”
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- Authors
- Tagliapietra, M.
- Affiliations
- University of Verona (IT)
- Corresponding author
- Tagliapietra, Matteo
- ORCID
- Tagliapietra, Matteo
- Venue
- Drugs of Today
- Publisher
- Portico
- Published
- 2022-10
- Volume
- 58
- Issue
- 10
- Pages
- 465-477
- ISSN
- 0025-7656 (ISSN-L)
- 1699-3993
- 1699-4019
- OpenAlex
- W4307839310
- Cited by
- 24
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 7 · 2023: 9 · 2022: 2 · 2021: 2
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drugs of today (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- aducanumab, Alzheimer's disease, amyloid-beta, anti-amyloid monoclonal antibodies, amyloid-related imaging abnormalities, accelerated FDA approval, clinical trial results, amyloid clearance, treatment-related adverse events, mild Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Humans, Amyloid beta-Peptides, Antibodies, Monoclonal, Humanized
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