Bapineuzumab and solanezumab for Alzheimer's disease: is the ‘amyloid cascade hypothesis’ still alive?
Abstract
INTRODUCTION: The 'amyloid cascade hypothesis' remains the leading hypothesis to explain the pathophysiology of Alzheimer's disease (AD). Immunotherapeutic agents have been developed to remove the neurotoxic amyloid β42 protein and prevent the hypothesized amyloid β42-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab. AREAS COVERED: This article briefly reviews the experimental agents in development for treatment of AD and then discusses the results of bapineuzumab and solanezumab in AD patients, as reported in preclinical studies, clinical trials and press releases. EXPERT OPINION: Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. However, analysis of pooled data from both trials showed a significant reduction in cognitive decline in mild AD patients. The improvement was associated with an increase in plasma amyloid-β (Aβ) levels and a low incidence of ARIA in solanezumab-treated patients. The marginal benefits of solanezumab are encouraging to support continued evaluation in future studies, and offer small support in favor of the ongoing viability of the 'amyloid cascade hypothesis' of AD.
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Clinical trials of the Aβ-directed mAb Bapineuzumab showed no clear cognitive benefits in patients with mild to moderate AD.
“Although clinical trials of the Aβ-directed mAb Bapinezumab showed no clear cognitive benefits in patients with mild to moderate AD [42], the results also indicated that APOE ε4 carrier status may limit the response to anti-Aβ passive immunization [43,44], as well as being associated with an increased rate of microbleeds and vasogenic edema [45].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [42]
The other antibody did not show a straightforward reduction in plaque burden.
“The other did not show a straightforward reduction in plaque burden, but despite this a subsequent alternative analysis argued clinical effects should not be ruled out and called for further studies [254].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [254]
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References 72 · Cited by 119
- Authors
- Tayeb, H. O., Murray, E. D., Price, B. H., & Tarazi, F. I.
- Affiliations
- Harvard University (US)
- Venue
- Expert Opinion on Biological Therapy
- Publisher
- Informa UK Limited
- Published
- 2013-04-10
- Volume
- 13
- Issue
- 7
- Pages
- 1075-1084
- ISSN
- 1471-2598 (ISSN-L)
- 1744-7682
- OpenAlex
- W2053936304
- Cited by
- 119
- References
- 72
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 7 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 18 · 2016: 19 · 2015: 11 · 2014: 17 · 2013: 14
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Update notices
- correction (2026-09-07)
- Open access
- closed
- Locations
- Expert Opinion on Biological Therapy (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
- Alzheimer's disease, amyloid hypothesis, bapineuzumab, solanezumab, amyloid-beta 42, anti-amyloid therapy, amyloid-related imaging abnormalities, cognitive decline, anti-amyloid monoclonal antibodies
- MeSH terms
- Alzheimer Disease, Animals, Humans, Immunotherapy, Antibodies, Monoclonal, Humanized
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