Cited by 965Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease

Panza, Francesco, Lozupone, Madia, Logroscino, Giancarlo, Imbimbo, Bruno P.·2019·Nature Reviews Neurology

DOI 10.1038/s41582-018-0116-6

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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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Result

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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
ORCID: Panza, Francesco
Lozupone, Madia
Logroscino, Giancarlo
Imbimbo, Bruno P.
Venue: Nature Reviews Neurology
Publisher: Springer Science and Business Media LLC
Published: 2019-01-04
Volume: 15
Issue: 2
Pages: 73-88
ISSN: 1759-4758 (ISSN-L)
1759-4766
DOI: 10.1038/s41582-018-0116-6
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease

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