Impact of Anti-amyloid-β Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer's Disease: A Focus on Aducanumab and Lecanemab
- PMID: 35493943
- PMCID: PMC9039457
- DOI: 10.3389/fnagi.2022.870517
Impact of Anti-amyloid-β Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer's Disease: A Focus on Aducanumab and Lecanemab
Abstract
Alzheimer's disease (AD) is the most prevalent form of age-related dementia in the world, and its main pathological features consist of amyloid-β (Aβ) plaque deposits and neurofibrillary tangles formed by hyperphosphorylated tau protein. So far, only a few AD treatments approved have been applied in the clinic, but the effects of these drugs are limited only for partial symptomatic relief to patients with AD and are unable to alter AD progression. Later, all efforts for AD treatments with targeting the pathogenic factors were unsuccessful over the past decades, which suggested that the pathogenesis of AD is complex. Recently, disease-modifying therapies (DMTs) that can change the underlying pathophysiology of AD, with anti-Aβ monoclonal antibodies (mabs) (e.g., aducanumab, bapineuzumab, gantenerumab, solanezumab, and lecanemab) have been developed successively and conducted in clinical trials based on the theory that a systemic failure of cell-mediated Aβ clearance contributes to AD occurrence and progression. In the review, we summarized recent studies on the therapeutic effects and clinical trial results of these mabs in patients with AD. Specifically, we focused on the discussion of the impact of aducanumab and lecanemab on AD pathology and clinical profiles. The review provides a possible evidence for applying immunotherapy with anti-Aβ mabs in AD and analyzes lessons learned from these clinical trials in order to further study the therapeutic and adverse effects of these anti-Aβ mabs on AD.
Keywords: Alzheimer’s disease; aducanumab; amyloid-β; lecanemab; monoclonal antibodies; treatment.
Copyright © 2022 Shi, Chu, Zhu and Zhu.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
-
- Abushakra S., Porsteinsson A., Scheltens P., Sadowsky C., Vellas B., Cummings J., et al. (2017). Clinical effects of tramiprosate in APOE4/4 homozygous patients with mild alzheimer’s disease suggest disease modification potential. J. Prev. Alzheimers Dis. 4 149–156. 10.14283/jpad.2017.26 - DOI - PubMed
-
- Abushakra S., Porsteinsson A., Vellas B., Cummings J., Gauthier S., Hey J. A., et al. (2016). Clinical benefits of tramiprosate in alzheimer’s disease are associated with higher number of APOE4 alleles: the “APOE4 gene-dose effect”. J. Prev. Alzheimers Dis. 3 219–228. 10.14283/jpad.2016.115 - DOI - PubMed
-
- Alexiou A., Chatzichronis S., Ashraf G. M. (2020). “Prediction of Alzheimer’s disease,” in Diagnosis and Management in Dementia, eds Martin C. R., Preedy V. R. (Boston: Academic Press; ), 365–378.
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