If amyloid drives Alzheimer disease, why have anti-amyloid therapies not yet slowed cognitive decline?
Open accessAbstract
Strong genetic evidence supports an imbalance between production and clearance of amyloid β-protein (Aβ) in people with Alzheimer disease (AD). Microglia that are potentially involved in alternative mechanisms are actually integral to the amyloid cascade. Fluid biomarkers and brain imaging place accumulation of Aβ at the beginning of molecular and clinical changes in the disease. So why have clinical trials of anti-amyloid therapies not provided clear-cut benefits to patients with AD? Can anti-amyloid therapies robustly decrease Aβ in the human brain, and if so, could this lowering be too little, too late? These central questions in research on AD are being urgently addressed.
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Lowering amyloid levels may help lessen the disease's related neurodegeneration and cognitive impairment.
“Lowering amyloid levels may help to lessen the disease’s related neurodegeneration and cognitive impairment, according to research [73,74].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [73]
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References 82 · Cited by 145
- Authors
- Haass, C., & Selkoe, D.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Brigham and Women's Hospital (US)
- Corresponding author
- Haass, Christian
- Selkoe, Dennis
- Venue
- PLOS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2022-07-21
- Volume
- 20
- Issue
- 7
- Pages
- e3001694
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC9302755
- OpenAlex
- W4286494256
- Cited by
- 145
- References
- 82
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 35 · 2023: 46 · 2022: 14 · 2020: 1
- FWCI
- 19.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- DZNE Pub (submittedVersion, cc-by)
- Funders
- DFG (EXC 2145 SyNergy – ID 390857198, HA1737/16-1)
- NIH (RF1 AG006173, P01 AG015379)
- David APP Fund at BWH
- 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-beta, anti-amyloid therapy, amyloid hypothesis, microglia, amyloid clearance, cognitive decline, clinical trial results, amyloid accumulation, fluid biomarkers, neuroimaging
- MeSH terms
- Alzheimer Disease, Amyloid, Amyloidosis, Brain, Humans, Amyloid beta-Peptides, Cognitive Dysfunction
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