Immunotherapy for Alzheimer’s disease: hoops and hurdles
Open accessAbstract
Alzheimer's disease (AD) is the most common form of dementia, afflicting more than 30 million people worldwide. Currently, there is no cure or way to prevent this devastating disease. Extracellular plaques, containing various forms of amyloid-β protein (Aβ), and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated tau protein, are two major pathological hallmarks of the AD brain. Aggregation, deposition, and N-terminal modification of Aβ protein and tau phosphorylation and aggregation are thought to precede the onset of cognitive decline, which is better correlated with tangle formation and neuron loss. Active and passive vaccines against various forms of Aβ have shown promise in pre-clinical animal models. However, translating these results safely and effectively into humans has been challenging. Recent clinical trials showed little or no cognitive efficacy, possibly due to the fact that the aforementioned neurodegenerative processes most likely pre-existed in the patients well before the start of immunotherapy. Efforts are now underway to treat individuals at risk for AD prior to or in the earliest stages of cognitive decline with the hope of preventing or delaying the onset of the disease. In addition, efforts to immunize against tau and other AD-related targets are underway.
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There is potential for differential responses to treatment among carriers of various APOE alleles in upcoming clinical trials targeting early and prodromal AD.
“As the intention of upcoming clinical trials of Aβ-directed therapeutics is to target patients with early and prodromal AD [46,47], there is still a potential for differential responses to treatment among carriers of various APOE alleles.”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [47]
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- Authors
- Lemere, C. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Lemere, Cynthia A
- ORCID
- Lemere, Cynthia A
- Venue
- Molecular Neurodegeneration
- Published
- 2013
- Volume
- 8
- Issue
- 1
- Pages
- 36
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC4015631
- OpenAlex
- W2116456562
- Cited by
- 196
- References
- 13
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 11 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 10 · 2019: 10 · 2018: 12 · 2017: 17 · 2016: 32 · 2015: 24 · 2014: 26 · 2013: 2
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (AG040092)
- National Institute on Aging (R01AG040092, AG040092)
- National Institute of Neurological Disorders and Stroke (R01NS136122)
- 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, immunotherapy, amyloid-beta, tau protein, amyloid plaques, neurofibrillary tangles, clinical trial translation, cognitive decline, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Humans, Immunotherapy, Alzheimer Vaccines
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