Abstract
Background: Meta-analyses show that copper non-bound to ceruloplasmin (non-Cp Cu, also known as ‘free’ copper) in serum is higher in a percentage of Alzheimer's disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp Cu cut-off sustains the existence of a copper AD metabolic subtype.
Objective: In order to find evidence of the existence of a detectable metabolic subtype of AD associated to copper abnormalities, we explore the hypothesis of a neuroimaging pattern heterogeneity in an homogenous and well characterized AD population classified in two groups by the stratification of patients on the basis non-Cp Cu cut-off.
Method: We assessed levels of copper, ceruloplasmin, non-Cp Cu, cerebrospinal levels of total Tau protein (h-tau), Thr 181 phosphorylated tau protein (P-tau) and β-amyloid 1-42, and APOE4 genotype in 66 AD patients and compared neuroimaging indices of a visual rating scale of cerebral atrophy and neurovascular burden in AD patients stratified in ‘Normal’ and ‘High’ non-Cp Cu groups.
Results: The stratification for non-Cp Cu originated AD groups which did not differ for medial temporal lobe atrophy, periventricular hyperintensities, deeper hyperintensities (including frontal, parietooccipital and temporal white matter hyperintensities), infratentorial hyperintensities indices, while they differed for global atrophy. More specifically, AD patients within the high non-Cp Cu group had a less severe burden of global atrophy (p=0.042).
Conclusion: This neuroimaging heterogeneity between AD groups is suggestive of the existence of a copper metabolic subtype of AD; non-Cp Cu appears a good marker of this copper AD.
Keywords: Neuroimaging heterogeneity, copper not bound to ceruloplasmin (non-Cp Cu), Alzheimer's disease, free copper, global atrophy, copper.
Current Alzheimer Research
Title:Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study
Volume: 14 Issue: 12
Author(s): Rosanna Squitti*, Ilaria Simonelli, Emanuele Cassetta, Domenico Lupoi, Mauro Rongioletti, Mariacarla Ventriglia and Mariacristina Siotto
Affiliation:
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio- Fatebenefratelli, 25125 Brescia,Italy
Keywords: Neuroimaging heterogeneity, copper not bound to ceruloplasmin (non-Cp Cu), Alzheimer's disease, free copper, global atrophy, copper.
Abstract: Background: Meta-analyses show that copper non-bound to ceruloplasmin (non-Cp Cu, also known as ‘free’ copper) in serum is higher in a percentage of Alzheimer's disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp Cu cut-off sustains the existence of a copper AD metabolic subtype.
Objective: In order to find evidence of the existence of a detectable metabolic subtype of AD associated to copper abnormalities, we explore the hypothesis of a neuroimaging pattern heterogeneity in an homogenous and well characterized AD population classified in two groups by the stratification of patients on the basis non-Cp Cu cut-off.
Method: We assessed levels of copper, ceruloplasmin, non-Cp Cu, cerebrospinal levels of total Tau protein (h-tau), Thr 181 phosphorylated tau protein (P-tau) and β-amyloid 1-42, and APOE4 genotype in 66 AD patients and compared neuroimaging indices of a visual rating scale of cerebral atrophy and neurovascular burden in AD patients stratified in ‘Normal’ and ‘High’ non-Cp Cu groups.
Results: The stratification for non-Cp Cu originated AD groups which did not differ for medial temporal lobe atrophy, periventricular hyperintensities, deeper hyperintensities (including frontal, parietooccipital and temporal white matter hyperintensities), infratentorial hyperintensities indices, while they differed for global atrophy. More specifically, AD patients within the high non-Cp Cu group had a less severe burden of global atrophy (p=0.042).
Conclusion: This neuroimaging heterogeneity between AD groups is suggestive of the existence of a copper metabolic subtype of AD; non-Cp Cu appears a good marker of this copper AD.
Export Options
About this article
Cite this article as:
Squitti Rosanna *, Simonelli Ilaria, Cassetta Emanuele , Lupoi Domenico , Rongioletti Mauro , Ventriglia Mariacarla and Siotto Mariacristina , Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study, Current Alzheimer Research 2017; 14 (12) . https://dx.doi.org/10.2174/1567205014666170623125156
DOI https://dx.doi.org/10.2174/1567205014666170623125156 |
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
-
Mitochondrial Disorders in Adults
Current Molecular Medicine Cardiovascular Adverse Effects of Anti-Inflammatory Drugs
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Conference Report: The Myriad Pathways of Neurodegeneration Discussed at NEUROCON 2015
Current Aging Science P2Y Purinoceptors as Potential Emerging Therapeutical Target in Vascular Disease
Current Pharmaceutical Design Traumatic Brain Injury and Blood-Brain Barrier Cross-Talk
CNS & Neurological Disorders - Drug Targets Anti-HIV Drug Distribution to the Central Nervous System
Current Pharmaceutical Design Heat Shock Proteins as Suppressors of Accumulation of Toxic Prefibrillar Intermediates and Misfolded Proteins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Lewy Bodies: A Spectator or Salient Killer?
CNS & Neurological Disorders - Drug Targets Reperfusion Therapies in Acute Ischemic Stroke
Recent Patents on CNS Drug Discovery (Discontinued) Autism Spectrum Disorders: Etiology and Pharmacotherapy
Current Drug Therapy Socio-economic Aspects of Alzheimer's Disease
Current Alzheimer Research Retraction Notice to Role of Vitamin K2 in the Treatment of Postmenopausal Osteoporosis
Current Drug Safety Hippocampal Mean Diffusivity for the Diagnosis of Dementia and Mild Cognitive Impairment in Primary Care
Current Alzheimer Research Neurodegenerative Pathways in Alzheimer’s Disease: A Review
Current Neuropharmacology UCP2 and CFH Gene Variants with Genetic Susceptibility to Schizophrenia in Turkish Population
Endocrine, Metabolic & Immune Disorders - Drug Targets Metabolic Basis of Sporadic Alzeimer’s Disease. Role of Hormones Related to Energy Metabolism
Current Pharmaceutical Design Perspectives in Medicinal Chemistry: Focusing on the Link between Diabetes, Alzheimer's Disease and Cancer for the Discovery of New Medicines
Current Topics in Medicinal Chemistry Neurobiology and Genetics of Behavioural Syndromes of Alzheimers Disease
Current Alzheimer Research Erythrocyte Amyloid Beta Peptide Isoform Distributions in Alzheimer and Mild Cognitive Impairment
Current Alzheimer Research Multi-potent Natural Scaffolds Targeting Amyloid Cascade: In Search of Alzheimer's Disease Therapeutics
Current Topics in Medicinal Chemistry