Abstract
Background: The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. Methods and Findings: AD patients aged 50 – 85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellmans colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by 10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2% increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. Conclusion: The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation.
Keywords: Acetylcholinesterase, Alzheimer's disease, Butyrylcholinesterase, Cerebrospinal fluid (CSF), Cholinesterase inhibitors
Current Alzheimer Research
Title: Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients
Volume: 6 Issue: 1
Author(s): Agneta Nordberg, Taher Darreh-Shori, Elaine Peskind, Hilkka Soininen, Malahat Mousavi, Gina Eagle and Roger Lane
Affiliation:
Keywords: Acetylcholinesterase, Alzheimer's disease, Butyrylcholinesterase, Cerebrospinal fluid (CSF), Cholinesterase inhibitors
Abstract: Background: The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. Methods and Findings: AD patients aged 50 – 85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellmans colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by 10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2% increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. Conclusion: The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation.
Export Options
About this article
Cite this article as:
Nordberg Agneta, Darreh-Shori Taher, Peskind Elaine, Soininen Hilkka, Mousavi Malahat, Eagle Gina and Lane Roger, Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients, Current Alzheimer Research 2009; 6 (1) . https://dx.doi.org/10.2174/156720509787313961
DOI https://dx.doi.org/10.2174/156720509787313961 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Neurobiology and Genetics of Behavioural Syndromes of Alzheimers Disease
Current Alzheimer Research Focusing on the Interactions between the GABAergic System and Neurosteroids in Neurodevelopmental Disorders
Current Pharmaceutical Design Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases
Current Medicinal Chemistry Mechanism of Tau-Induced Neurodegeneration in Alzheimer Disease and Related Tauopathies
Current Alzheimer Research Incidence and Prevalence of Hypothyroidism in Patients Affected by Chronic Heart Failure: Role of Amiodarone
Endocrine, Metabolic & Immune Disorders - Drug Targets Combination of Memantine and 6-Chlorotacrine as Novel Multi-Target Compound against Alzheimer’s Disease
Current Alzheimer Research Genomics and Natural Products: Role of Bioinformatics and Recent Patents
Recent Patents on Biotechnology Antiepileptic Drugs for the Treatment of Impulsivity
Current Psychiatry Reviews Intravenous Thrombolysis with rt-PA in Acute Stroke Patients Aged ≥80 Years
Letters in Drug Design & Discovery Defining Dystonic Tremor
Current Neuropharmacology Human Cognition Assessment in Drug Research
Current Pharmaceutical Design Cell Therapy for Stroke: Emphasis on Optimizing Safety and Efficacy Profile of Endothelial Progenitor Cells
Current Pharmaceutical Design Poly(ADP-Ribose) Polymerase Inhibitors: New Pharmacological Functions and Potential Clinical Implications
Current Pharmaceutical Design Gender Differences in Response to Therapy for Cardiovascular Diseases
Current Pharmacogenomics and Personalized Medicine New Promises to Cure Cancer and Other Genetic Diseases/Disorders: Epi-drugs Through Epigenetics
Current Topics in Medicinal Chemistry Nicotinic Receptors in Neurodegeneration
Current Neuropharmacology Syntheses of Ethyl Pyruvate’s Bioisosteres Inhibiting Inducible Nitric Oxide Production in Lipopolysaccharide-induced BV2 Cells
Letters in Drug Design & Discovery G Protein-Coupled Receptors: Target-Based In Silico Screening
Current Pharmaceutical Design Possible Role of Vascular Risk Factors in Alzheimer's Disease and Vascular Dementia
Current Pharmaceutical Design Diabetes Care: Risk Factors, Prediction, Prevention, and Individualized Treatment
Infectious Disorders - Drug Targets