Anti-Aβ Therapeutics in Alzheimer's Disease: The Need for a Paradigm Shift
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Most current Alzheimer's disease (AD) therapies in advanced phases of development target amyloid β-peptide (Aβ) production, aggregation, or accumulation. Translational models suggest that anti-Aβ therapies may be highly effective if tested as agents to prevent or delay development of the disease or as therapies for asymptomatic patients with very early signs of AD pathology. However, anti-Aβ therapeutics are currently being tested in symptomatic patients where they are likely to be much less effective or ineffective. The lack of alignment between human clinical studies and preclinical studies, together with predictions about optimal trial design based on our understanding of the initiating role of Aβ aggregates in AD, has created a treatment versus prevention dilemma. In this perspective, we discuss why it is imperative to resolve this dilemma and suggest ways for moving forward in the hopes of enhancing the development of truly effective AD therapeutics.
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Multiple lines of evidence indicate that aberrant Aβ production or clearance is an early component in the pathogenesis of Alzheimer's disease.
“Multiple lines of evidence indicate that aberrant Aβ production or clearance is an early component in the pathogenesis of Alzheimer’s disease.1–3”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [3]
The causes and compelling drug targets for Alzheimer disease are not sufficiently known.
“The formidable challenges to preventing clinical and pathological AD include that the causes and compelling drug targets are not sufficiently known, despite the importance, intense focus, and highly developed science of the amyloid-|3 cascade (7).”
From Recruitment methods for united states Alzheimer disease prevention trials (2012) · cites this paper as [7]
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Self-citation
- Authors
- Golde, T. E., Schneider, L. S., & Koo, E. H.
- Affiliations
- University of Florida (US)
- University of Southern California (US)
- University of California San Diego (US)
- Corresponding author
- Golde, Todd E.
- Schneider, Lon S.
- Koo, Edward H.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 69
- Issue
- 2
- Pages
- 203-213
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3058906
- OpenAlex
- W2045311514
- Cited by
- 382
- References
- 74
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 10 · 2023: 10 · 2022: 14 · 2021: 22 · 2020: 18 · 2019: 25 · 2018: 20 · 2017: 26 · 2016: 32 · 2015: 31 · 2014: 40 · 2013: 40 · 2012: 59
- FWCI
- 36.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 928 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Abbott Laboratories
- AstraZeneca
- Myriad Genetics
- H. Lundbeck A/S
- National Institute on Aging (AG 05142, AG020206, R01AG018454, P01AG020206, P50AG005142)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, amyloid-beta, anti-amyloid therapy, amyloid fibril formation, prevention versus treatment, early Alzheimer's disease, clinical trial design, preclinical to clinical translation, symptomatic versus asymptomatic patients
- MeSH terms
- Alzheimer Disease, Clinical Trials as Topic, Health Services Needs and Demand, Humans, Biomarkers, Amyloid beta-Peptides, Disease Progression, Apolipoprotein E4, Translational Research, Biomedical
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