The role of acetylcholinesterase in the pathogenesis of Alzheimer's disease
Abstract
Treatment of Alzheimer's disease has been dominated by the use of acetylcholinesterase (AChE) inhibitors. These drugs compensate for the death of cholinergic neurons and offer symptomatic relief by inhibiting acetylcholine (ACh) turnover and restoring synaptic levels of this neurotransmitter. Recently, however, AChE itself has been implicated in the pathogenesis of Alzheimer's disease. In particular, it appears that AChE may directly interact with amyloid-beta in a manner that increases the deposition of this peptide into insoluble plaques. This new role suggests that properly designed AChE inhibitors might be able to act as disease-modifying agents rather than as mere palliatives. Additionally, numerous studies have suggested that cholinergic modulation and other functional consequences of AChE inhibition may affect amyloid precursor protein processing and protect neurons against a variety of insults. It therefore seems likely that new AChE inhibitors, which capitalize on all these strengths would be excellent candidates for future Alzheimer's disease therapy.
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Increasing acetylcholine concentration at the synapse by inhibiting AChE is one approach to slow down the progression of AD.
“An increase of acetylcholine concentration (ACh) at the synapse by inhibiting the acetylcholinesterase (AChE) is one of the approaches to slow down the progression of AD [18,19,20,21,22,23,24,25,26].”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [19]
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Hussain, R., Rahim, F., Rehman, W. U., Taha, M., Khan, S., Zaman, K., Shah, S. A. A., Wadood, A., Imran, S., & Abdellattif, M. H. (2022) · Chemistry & Biodiversity · doi:10.1002/cbdv.202200323 · Cited by 9 · see citing works
“[7–9] From the detail study showed that acetylcholinesterase (AChE) and beta-secretase (BACE-1) are the alluring drug targets that attracted much attention among others, and play vital role in Alzheimer’s pathogenesis, responsible for the defects in the cholinergic signaling pathway([10]) and the formation of beta-amy…”
BackgroundEl‐Hussieny, M., El‐Mansy, M. F., Ewies, E. F., et al. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.134214 · Cited by 9 · see citing works
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Novel pyrazinamide condensed azetidinones inhibit the activities of cholinesterase enzymes
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Singh, A. A., Khan, F., & Song, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104707 · Cited by 8 · see citing works
“These medications restore synaptic levels of ACh and restrict its turnover, compensating for the loss of cholinergic neurons and providing symptomatic relief [15].”
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Potential Anti-Alzheimer Properties of Mogrosides in Vitamin B12-Deficient Caenorhabditis elegans
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“The human AChE homolog is known to be involved in the pathogenesis of AD [39].”
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“AChE inhibitors, such as tacrine (THA), donepezil, galantamine, and rivastigmine (Figure 1) have been approved for AD symptomatic treatment by reducing AChE activity [9].”
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Dianas farmacológicas en las enfermedades neurodegenerativas
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“Fármacos inhibidores del catabolismo de la acetilcolina [6], inhibidores de la acetilcolinesterasa, como la tacrina, el donepezilo, la rivastigmina y la galantamina.”
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“This is evidenced by the use of acetylcholinesterase inhibitors in the treatment of AD (Lane et al. 2006; Rees and Brimijoin 2003).”
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“Thus, inhibiting the activity of acetylcholinesterase (AChE), an enzyme that catalyzes the hydrolysis of ACh, is considered one of the key molecular targets for treating AD (Rees & Brimijoin, 2003).”
BackgroundGaber, S. A. A., Hamza, A. H., Tantawy, M. A., Toraih, E. A., & Ahmed, H. H. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15051386 · Cited by 6 · see citing works
“Additionally, AchE is known to act as an amyloidogenic factor supporting the deposition of tau protein and augmenting its correlated neurotoxicity [69].”
Background
- Authors
- Rees, T. M., & Brimijoin, S.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Brimijoin, S.
- Venue
- Drugs of today
- Publisher
- Portico
- Published
- 2003
- Volume
- 39
- Issue
- 1
- Pages
- 75
- ISSN
- 0025-7656 (ISSN-L)
- 1699-4019
- OpenAlex
- W1966053837
- Cited by
- 171
- References
- 0
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 23 · 2023: 25 · 2022: 25 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drugs of today (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 16574, P50AG016574)
- 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, Alzheimer's disease pathogenesis, acetylcholinesterase inhibitors, amyloid-beta deposition, amyloid plaques, cholinergic neurons, APP processing, disease-modifying therapy, acetylcholine neurotransmission
- MeSH terms
- Acetylcholinesterase, Alzheimer Disease, Animals, Cholinesterase Inhibitors, Humans
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