Abstract
Alzheimers disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline associated with a deficit in cholinergic function. Inhibitors of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE), such as donepezil, galantamine or rivastigmine, are widely prescribed as symptomatic treatments for AD. These agents exhibit a wide variation in their pharmacological properties. Here we review clinical data from 1998 to 2009 investigating the effects of different cholinesterase inhibitor treatments on the levels and activities of cholinesterases in the cerebrospinal fluid (CSF) of AD patients. These studies suggest that treatment with rapidly-reversible cholinesterase inhibitors (e.g. donepezil, galantamine, tacrine) is associated with marked and significant upregulation of AChE activities and protein levels in the CSF of AD patients. In contrast, pseudo-irreversible cholinesterase inhibition (e.g. rivastigmine) is associated with a significant decrease in both CSF AChE and BuChE activities, with no upregulation of CSF protein levels. Additionally, donepezil is associated with a decrease in the level of the AChE-R isoform relative to the synaptic AChE-S isoform, whereas rivastigmine seems to increase this ratio. These findings suggest that these agents exert different effects on CSF cholinesterases. The clinical effects of these pharmacological differences are yet to be fully established.
Keywords: Cholinesterase inhibitors, Alzheimer's disease, cerebrospinal fluid, acetylcholinesterase, butyrylcholinesterase
Current Alzheimer Research
Title: Effects of Cholinesterase Inhibitors on the Activities and Protein Levels of Cholinesterases in the Cerebrospinal Fluid of Patients with Alzheimers Disease: A Review of Recent Clinical Studies
Volume: 7 Issue: 1
Author(s): T. Darreh-Shori and H. Soininen
Affiliation:
Keywords: Cholinesterase inhibitors, Alzheimer's disease, cerebrospinal fluid, acetylcholinesterase, butyrylcholinesterase
Abstract: Alzheimers disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline associated with a deficit in cholinergic function. Inhibitors of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE), such as donepezil, galantamine or rivastigmine, are widely prescribed as symptomatic treatments for AD. These agents exhibit a wide variation in their pharmacological properties. Here we review clinical data from 1998 to 2009 investigating the effects of different cholinesterase inhibitor treatments on the levels and activities of cholinesterases in the cerebrospinal fluid (CSF) of AD patients. These studies suggest that treatment with rapidly-reversible cholinesterase inhibitors (e.g. donepezil, galantamine, tacrine) is associated with marked and significant upregulation of AChE activities and protein levels in the CSF of AD patients. In contrast, pseudo-irreversible cholinesterase inhibition (e.g. rivastigmine) is associated with a significant decrease in both CSF AChE and BuChE activities, with no upregulation of CSF protein levels. Additionally, donepezil is associated with a decrease in the level of the AChE-R isoform relative to the synaptic AChE-S isoform, whereas rivastigmine seems to increase this ratio. These findings suggest that these agents exert different effects on CSF cholinesterases. The clinical effects of these pharmacological differences are yet to be fully established.
Export Options
About this article
Cite this article as:
Darreh-Shori T. and Soininen H., Effects of Cholinesterase Inhibitors on the Activities and Protein Levels of Cholinesterases in the Cerebrospinal Fluid of Patients with Alzheimers Disease: A Review of Recent Clinical Studies, Current Alzheimer Research 2010; 7 (1) . https://dx.doi.org/10.2174/156720510790274455
DOI https://dx.doi.org/10.2174/156720510790274455 |
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
-
Recent Advances in Nanoneurology for Drug Delivery to the Brain
Current Nanoscience Neuroimmune Crosstalk in CNS Disorders: The Histamine Connection
Current Pharmaceutical Design Development and Validation of Microbiological Assay for Ceftriaxone and its Application in Photo-stability Study
Current Pharmaceutical Analysis CD93: Recent Advances and Implications in Disease
Current Drug Targets Association Between Seizures and Diabetes Mellitus: A Comprehensive Review of Literature
Current Diabetes Reviews Antibiotic Treatment in Native Valve Infective Endocarditis
Infectious Disorders - Drug Targets The Antibiotic Potential of Prokaryotic IMP Dehydrogenase Inhibitors
Current Medicinal Chemistry Dipeptidyl Peptidase-4 (CD26): Knowing the Function before Inhibiting the Enzyme
Current Medicinal Chemistry Complications of Serogroup B Meningococcal Disease in Survivors: A Review
Infectious Disorders - Drug Targets Silicosis in Current Scenario: A Review of Literature
Current Respiratory Medicine Reviews Therapeutic Targets for the Prevention of Type 1 Diabetes Mellitus
Current Drug Targets - Immune, Endocrine & Metabolic Disorders New Perspectives of Infections in Cardiovascular Disease
Current Cardiology Reviews Ligands and Therapeutic Perspectives of Adenosine A2A Receptors
Current Pharmaceutical Design Tumor-Associated Macrophages as Potential Targets for Anti-Cancer Activity of Marine Invertebrate-Derived Compounds
Current Pharmaceutical Design Drug Targets of Migraine and Neuropathy: Treatment of Hyperexcitability
CNS & Neurological Disorders - Drug Targets Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice
Current Reviews in Clinical and Experimental Pharmacology Individual Triptan Selection in Migraine Attack Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Abeta Immunotherapy and Other Means to Remove Amyloid
Current Drug Targets - CNS & Neurological Disorders Synthesis and Antibacterial Activity of New Chalcones Bearing an Imidazo[ 1,2-a]pyridine Moiety
Current Chemical Biology Short- and Long-Term Survival of Nonsurgical Intensive Care Patients and its Relation to Diagnosis, Severity of Disease, Age and Comorbidities
Current Aging Science