Acetylcholinesterase inhibitors for Alzheimer’s disease: anti-inflammatories in acetylcholine clothing!
Abstract
The pathogenesis of Alzheimer's disease (AD) has been linked to a deficiency in the brain neurotransmitter acetylcholine. Subsequently, acetylcholinesterase inhibitors (AChEIs) were introduced for the symptomatic treatment of AD. The prevailing view has been that the efficacy of AChEIs is attained through their augmentation of acetylcholine-medicated neuron to neuron transmission. However, AChEIs also protect cells from free radical toxicity and beta-amyloid-induced injury, and increased production of antioxidants. In addition, it has been reported that AChEIs directly inhibit the release of cytokines from microglia and monocytes. These observations are supported by evidence showing a role for acetylcholine in suppression of cytokine release through a 'cholinergic anti-inflammatory pathway'. Based on the accumulating research data so far, it is no longer appropriate to consider that the sole action of AChEIs in AD is through direct acetylcholine-medicated enhancement of neuronal transmission. Evidence points to a possible anti-inflammatory role for these agents as well.
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Acetylcholinesterase inhibitors work by blocking acetylcholinesterase, which boosts acetylcholine levels in the brains of individuals with mild to moderate Alzheimer's disease.
“These medications work by blocking the enzyme acetylcholinesterase, which is crucial for the metabolic breakdown of acetylcholine, which results in boosting its level in the brains of individuals with mild to moderate AD.”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Tabet, 2006
In most patients, acetylcholinesterase inhibitors were noted to be well tolerated.
“In most patients, these classes of drugs were noted to be well tolerated (Tabet, 2006).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Tabet, 2006
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The present and future of pharmacotherapy of Alzheimer's disease: a comprehensive review
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- Authors
- Tabet, N.
- Affiliations
- University of Brighton (GB)
- Corresponding author
- Tabet, N.
- ORCID
- Tabet, N.
- Venue
- Age and Ageing
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07-01
- Volume
- 35
- Issue
- 4
- Pages
- 336-338
- ISSN
- 0002-0729 (ISSN-L)
- 1468-2834
- OpenAlex
- W2134267412
- Cited by
- 285
- References
- 27
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 19 · 2023: 21 · 2022: 18 · 2021: 25 · 2020: 14 · 2019: 24 · 2018: 23 · 2017: 13 · 2016: 12 · 2015: 17 · 2014: 18 · 2013: 27 · 2012: 12
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Age and Ageing (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- acetylcholinesterase inhibitors, Alzheimer's disease, cholinergic anti-inflammatory pathway, acetylcholine, neuroinflammation, cytokine production, microglia, monocytes, free radical toxicity, amyloid-beta, antioxidants, neural transmission
- MeSH terms
- Acetylcholine, Aged, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Cholinesterase Inhibitors, Humans, Cytokines, Neurotransmitter Agents
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