The DOI matches its Crossref record; 221 of the 221 references it cites were found in a registry or an index.
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Abstract
Brain accumulation of the amyloid-β (Aβ) peptide is believed to be the initial event in the Alzheimer disease (AD) process. Aβ accumulation begins 15-20 years before clinical symptoms occur, mainly owing to defective brain clearance of the peptide. Over the past 20 years, we have seen intensive efforts to decrease the levels of Aβ monomers, oligomers, aggregates and plaques using compounds that decrease production, antagonize aggregation or increase brain clearance of Aβ. Unfortunately, these approaches have failed to show clinical benefit in large clinical trials involving patients with mild to moderate AD. Clinical trials in patients at earlier stages of the disease are ongoing, but the initial results have not been clinically impressive. Efforts are now being directed against Aβ oligomers, the most neurotoxic molecular species, and monoclonal antibodies directed against these oligomers are producing encouraging results. However, Aβ oligomers are in equilibrium with both monomeric and aggregated species; thus, previous drugs that efficiently removed monomeric Aβ or Aβ plaques should have produced clinical benefits. In patients with sporadic AD, Aβ accumulation could be a reactive compensatory response to neuronal damage of unknown cause, and alternative strategies, including interference with modifiable risk factors, might be needed to defeat this devastating disease.
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In the citing paper
“The concentration of amyloid in the brain is associated with the risk and progression of dementia.”
From Endpoints for geroscience clinical trials: health outcomes, biomarkers, and biologic age (2022) · cites this paper as [16]
In the citing paper
“Consistently, trials that have found that reduction in brain amyloid have failed to have beneficial effects on cognitive function or risk of dementia [16].”
From Endpoints for geroscience clinical trials: health outcomes, biomarkers, and biologic age (2022) · cites this paper as [16]
In the citing paper
“Missing relevant Aβ structures as possible therapeutic targets might be one of the reasons why anti-Aβ strategies developed to fight AD have not yet demonstrated significant clinical benefits (Panza et al., 2019)”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Panza et al., 2019
In the citing paper
“Many amyloid-β lowering approaches have failed [31].”
From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [31]
In the citing paper
“Studies have shown that Aβ buildup can start 15–20 years before clinical symptoms appear, indicating that therapy effectiveness may depend on early intervention [88,89].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [88]
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Metadata
- Authors
- Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P.
- Affiliations
- Casa Sollievo della Sofferenza (IT)
- University of Bari Aldo Moro (IT)
- Chiesi (Italy) (IT)
- Corresponding author
- Panza, Francesco
- Venue
- Nature Reviews Neurology
- Published
- 2019-01-04
- Volume
- 15
- Issue
- 2
- Pages
- 73-88
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W2907547898
- Cited by
- 965
- References
- 221
- Citations by year
- 2026: 58 · 2025: 103 · 2024: 117 · 2023: 151 · 2022: 141 · 2021: 154 · 2020: 176 · 2019: 64
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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-beta, amyloid-beta oligomers, amyloid-beta clearance, amyloid plaques, monoclonal antibodies, disease-modifying therapy, clinical trial failure, sporadic Alzheimer's disease, risk factor control
- MeSH terms
- Alzheimer Disease, Animals, Humans, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Drug Delivery Systems, Amyloid Precursor Protein Secretases, Antibodies, Monoclonal, Humanized
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