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Cited by 351Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease

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Nordberg, Agneta, Ballard, Clive, Bullock, Roger, Darreh-Shori, Taher, Somogyi, Monique·2013·The Primary Care Companion For CNS Disorders
DOI 10.4088/pcc.12r01412PMC PMC3733526
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Abstract

OBJECTIVE: To examine the role of butyrylcholinesterase (BuChE) in cholinergic signaling and neurologic conditions, such as Alzheimer's disease (AD). The rationale for inhibiting cholinesterases in the management of AD, including clinical evidence supporting use of the dual acetylcholinesterase (AChE) and BuChE inhibitor rivastigmine, is discussed. DATA SOURCES: PubMed searches were performed using butyrylcholinesterase as a keyword. English-language articles referenced in PubMed as of September 2011 were included. Study Selection and Data Synthesis: English-language articles related to BuChE considered to be of clinical relevance to physicians were included. English-language articles specifically related to AChE were not included, as the role of AChE in cholinergic signaling and the underlying pathology of AD is well documented. Reference lists of included publications were used to supplement the search. RESULTS: AChE and BuChE play a role in cholinergic signaling; BuChE can hydrolyze acetylcholine and compensate for AChE when levels are depleted. In the AD brain, AChE levels decrease, while BuChE levels are reportedly increased or unchanged, with changes becoming more pronounced during the disease course. Furthermore, BuChE genotype may influence AD risk and rate of disease progression. Strategies that increase acetylcholine levels (eg, cholinesterase inhibitors) demonstrate symptomatic efficacy in AD. Rivastigmine has proven cognitive efficacy in clinical trials, and data suggest that its action is mediated, in part, by inhibition of BuChE. Retrospective analyses of clinical trials provide evidence that BuChE genotype may also influence treatment response. CONCLUSIONS: AChE-selective inhibitors and a dual AChE and BuChE inhibitor demonstrate symptomatic efficacy in AD. Mounting preclinical and clinical evidence for a role of BuChE in maintaining normal cholinergic function and the pathology of AD provides a rationale for further studies investigating use of rivastigmine in AD and the influence of BuChE genotype on observed efficacy.

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  • AChE is typically elevated in Alzheimer's disease patients, especially in the cortex and hippocampus, contributing to cognitive impairment.

    “AChE, responsible for the breakdown of ACh, is typically elevated in AD patients, especially in the cortex and hippocampus, contributing to cognitive impairment.”

    From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [7]

    The Results section on cholinesterase activity says AChE activity is decreased, not typically elevated, in certain AD brain regions. The section on expression also reports decreases in synaptic AChE and in a major AChE form in the hippocampus and cortex. Page numbers were not supplied. (LLM, conf=0.93)

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  • BuChE, although less prominent in healthy brains, increases in Alzheimer's disease, particularly in regions affected by amyloid pathology, potentially compensating for the loss of cholinergic neurons.

    “BuChE, although less prominent in healthy brains, increases in AD, particularly in regions affected by amyloid pathology, potentially compensating for the loss of cholinergic neurons [6,7].”

    From Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review (2025) · cites this paper as [7]

    The Results section says AChE predominates in healthy brains, while BuChE activity in AD is increased or unchanged in certain regions and is associated with amyloid plaques. It also describes cholinergic-neuron loss, but says BuChE may compensate for depleted AChE—not specifically for the loss of those neurons. The claim therefore overstates both the consistency of the increase and the proposed compensation. (LLM, conf=0.86)

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Research works printed but not linked: 11

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Authors
Nordberg, A., Ballard, C., Bullock, R., Darreh-Shori, T., & Somogyi, M.
Affiliations
King's College London (GB)
Corresponding author
Nordberg, Agneta
ORCID
Venue
The Primary Care Companion For CNS Disorders
Publisher
Physicians Postgraduate Press, Inc
Published
2013-03-07
Volume
15
Issue
2
ISSN
  • 2155-7772 (ISSN-L)
  • 2155-7780
DOI
10.4088/pcc.12r01412
PMC
PMC3733526
OpenAlex
W176570333
Cited by
323
References
120
Citations by year
2026: 20 · 2025: 21 · 2024: 39 · 2023: 20 · 2022: 35 · 2021: 33 · 2020: 38 · 2019: 28 · 2018: 32 · 2017: 21 · 2016: 19 · 2015: 7 · 2014: 8 · 2013: 1
FWCI
9.07
Type
journal article
Language
en
Open access
Locations
  • The Primary Care Companion For CNS Disorders (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
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
butyrylcholinesterase, Alzheimer's disease, rivastigmine, cholinesterase inhibitors, acetylcholinesterase, cholinergic neurotransmission, acetylcholine hydrolysis, treatment response, disease progression

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