Abstract
Background: Previous studies have demonstrated alterations in the peripheral cholinergic system in Alzheimer's disease (AD), though results have been inconsistent and not linked to in vivo biomarkers of pathology. We examined the relationship between amyloid-beta (Aβ) plaques and plasma cholinesterase activity in a heterogeneous dementia population. Methods: 29 participants with clinical AD and 35 with non-AD diagnoses underwent positron emission tomography (PET) with the amyloid ligand [11C] PIB and plasma measurements of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Multi-linear regression was used to evaluate the relationship between AChE or BChE activity and PIB binding (adjusted for age, sex, apolipoprotein E4 and vascular risk), applying voxel-wise and region of interest (ROI) approaches. AChE activity was further adjusted for cholinesterase inhibitor (ChE-I) use. Global amyloid load was measured using a PIB Index, representing mean tracer binding in frontal, parietal, lateral temporal and cingulate cortex. Results: AChE activity was correlated with PIB Index (β=0.39, p<0.001) and with regional PIB binding in frontal, temporal, parietal and occipital lobes, precuneus and posterior cingulate on both voxel-wise (p<0.001 uncorrected) and ROI (β=0.26-0.41, p<0.005) analysis. Correlations remained significant after covarying clinical diagnosis (β=0.42, p=0.001), and among participants naive to ChE-I (β=0.51, p=0.005). No correlation was found between BChE activity and PIB. Among AD participants, disease severity was not correlated with AChE, BChE or PIB Index. Conclusion: AChE activity in plasma is correlated with brain Aβ load. Activation of the 'anti-inflammatory cholinergic pathway' may provide the link between Aβ plaques and peripheral cholinergic measures.
Keywords: Amyloid- β, Pittsburgh Compound-B, amyloid imaging, plasma acetylcholinesterase, plasma butyrylcholinesterase
Current Alzheimer Research
Title:Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load
Volume: 10 Issue: 1
Author(s): Adi Alkalay, Gil D. Rabinovici, Gabriel Zimmerman, Neha Agarwal, Daniela Kaufer, Bruce L. Miller, William J Jagust and Hermona Soreq
Affiliation:
Keywords: Amyloid- β, Pittsburgh Compound-B, amyloid imaging, plasma acetylcholinesterase, plasma butyrylcholinesterase
Abstract: Background: Previous studies have demonstrated alterations in the peripheral cholinergic system in Alzheimer's disease (AD), though results have been inconsistent and not linked to in vivo biomarkers of pathology. We examined the relationship between amyloid-beta (Aβ) plaques and plasma cholinesterase activity in a heterogeneous dementia population. Methods: 29 participants with clinical AD and 35 with non-AD diagnoses underwent positron emission tomography (PET) with the amyloid ligand [11C] PIB and plasma measurements of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Multi-linear regression was used to evaluate the relationship between AChE or BChE activity and PIB binding (adjusted for age, sex, apolipoprotein E4 and vascular risk), applying voxel-wise and region of interest (ROI) approaches. AChE activity was further adjusted for cholinesterase inhibitor (ChE-I) use. Global amyloid load was measured using a PIB Index, representing mean tracer binding in frontal, parietal, lateral temporal and cingulate cortex. Results: AChE activity was correlated with PIB Index (β=0.39, p<0.001) and with regional PIB binding in frontal, temporal, parietal and occipital lobes, precuneus and posterior cingulate on both voxel-wise (p<0.001 uncorrected) and ROI (β=0.26-0.41, p<0.005) analysis. Correlations remained significant after covarying clinical diagnosis (β=0.42, p=0.001), and among participants naive to ChE-I (β=0.51, p=0.005). No correlation was found between BChE activity and PIB. Among AD participants, disease severity was not correlated with AChE, BChE or PIB Index. Conclusion: AChE activity in plasma is correlated with brain Aβ load. Activation of the 'anti-inflammatory cholinergic pathway' may provide the link between Aβ plaques and peripheral cholinergic measures.
Export Options
About this article
Cite this article as:
Alkalay Adi, D. Rabinovici Gil, Zimmerman Gabriel, Agarwal Neha, Kaufer Daniela, L. Miller Bruce, J Jagust William and Soreq Hermona, Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load, Current Alzheimer Research 2013; 10 (1) . https://dx.doi.org/10.2174/1567205011310010007
DOI https://dx.doi.org/10.2174/1567205011310010007 |
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
-
Antiplatelet Therapy in Acute Coronary Syndromes. Evidence Based Medicine
Current Pharmaceutical Design A Hydrazide Linker Strategy for Heterobivalent Compounds as Ortho- and Allosteric Ligands of Acetylcholine-Binding Proteins
Current Topics in Medicinal Chemistry Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD
Current Alzheimer Research Serpins for Diagnosis and Therapy in Cancer
Cardiovascular & Hematological Disorders-Drug Targets Post Dural Puncture Headache and Hypertension
Current Hypertension Reviews A Novel Finding: Macrophages Involved in Inflammation Participate in Acute Aortic Dissection Complicated with Acute Lung Injury
Current Molecular Medicine Acetylcholinesterase Imaging: Its Use in Therapy Evaluation and Drug Design
Current Pharmaceutical Design Preface
Current Medicinal Chemistry - Central Nervous System Agents Nitric Oxide Homeostasis in Neurodegenerative Diseases
Current Alzheimer Research Propofol Promotes Blood-Brain Barrier Breakdown and Heat Shock Protein (HSP 72 kd) Activation in the Developing Mouse Brain
CNS & Neurological Disorders - Drug Targets Genetic Factors in Parkinsons Disease and Potential Therapeutic Targets
Current Neuropharmacology Prevention of Cardiovascular Diseases with Anti-Inflammatory and Anti- Oxidant Nutraceuticals and Herbal Products: An Overview of Pre-Clinical and Clinical Studies
Recent Patents on Inflammation & Allergy Drug Discovery A Co-Module Regulated by Therapeutic Drugs in a Molecular Subnetwork of Alzheimer’s Disease Identified on the Basis of Traditional Chinese Medicine and SAMP8 Mice
Current Alzheimer Research Aptiom (Eslicarbazepine Acetate) as a Dual Inhibitor of β-Secretase and Voltage-Gated Sodium Channel: Advancement in Alzheimer's Disease-Epilepsy Linkage via an Enzoinformatics Study
CNS & Neurological Disorders - Drug Targets Detection of Mild Cognitive Impairment Based on Virtual Reality: A Scoping Review
Current Alzheimer Research Chemokines and Brain Functions
Current Drug Targets - Inflammation & Allergy Metacognition and Social Functioning in Schizophrenia: Evidence, Mechanisms of Influence and Treatment Implications
Current Psychiatry Reviews Is there a Possible Single Mediator in Modulating Neuroendocrine–thymus Interaction in Ageing?
Current Aging Science Hyperhomocysteinaemia: A Critical Review of Old and New Aspects
Current Drug Metabolism ISCHEMIRs: Finding a Way Through the Obstructed Cerebral Arteries
Current Drug Targets