Abstract
Mild cognitive impairment (MCI) is considered a nosological entity or a translational state between normal aging and sporadic Alzheimer´s disease (AD). From brain tissue to peripheral blood samples, it is evident that the early markers of metabolic dysfunction observed in AD have also been found in MCI subjects. These observations obtained from MCI and AD subjects leave open the possibility that mitochondrial dysfunction-induced oxidative damage happening a priori of symptom onset, may trigger other pathological hallmarks, namely Aβ oligomerization.
In this study, we used a citoplasmic hybrid (cybrid) model created by the repopulation of human teratocarcinoma (NT2) cells depleted of endogenous mitochondrial DNA (mtDNA) with platelets from age-matched controls, MCI and AD subjects. We found mitochondrial deficits in MCI and AD cybrids as compared with controls, such as a decrease in cytochrome c oxidase (COX) activity, a decrease in mitochondrial membrane potential and in mitochondrial cytochrome c content. Consequently, we analyzed parameters of oxidative damage and found that AD and MCI cybrids exhibit an increase in lipid peroxides, higher production of superoxide radicals, and higher content in protein carbonyls. Since our data clearly show alterations in mitochondrial-mediated oxidative damage in MCI cybrids we propose that mitochondrial dysfunction is an early event in idiopathic AD. Moreover, we found that mitochondrial Aβ oligomeric content increases in AD, which may exacerbate initial mitochondrial damage. Altogether, our data strongly supports a key role for mitochondria/ mtDNA in aged-driven AD pathology.Keywords: MCI cybrids, mitochondrial dysfunction, oxidative stress
Current Alzheimer Research
Title:Prodromal Metabolic Phenotype in MCI Cybrids: Implications for Alzheimer’s Disease
Volume: 10 Issue: 2
Author(s): D. F. Silva, I. Santana, A. R. Esteves, I. Baldeiras, D. M. Arduino, C. R. Oliveira and S. M. Cardoso
Affiliation:
Keywords: MCI cybrids, mitochondrial dysfunction, oxidative stress
Abstract: Mild cognitive impairment (MCI) is considered a nosological entity or a translational state between normal aging and sporadic Alzheimer´s disease (AD). From brain tissue to peripheral blood samples, it is evident that the early markers of metabolic dysfunction observed in AD have also been found in MCI subjects. These observations obtained from MCI and AD subjects leave open the possibility that mitochondrial dysfunction-induced oxidative damage happening a priori of symptom onset, may trigger other pathological hallmarks, namely Aβ oligomerization.
In this study, we used a citoplasmic hybrid (cybrid) model created by the repopulation of human teratocarcinoma (NT2) cells depleted of endogenous mitochondrial DNA (mtDNA) with platelets from age-matched controls, MCI and AD subjects. We found mitochondrial deficits in MCI and AD cybrids as compared with controls, such as a decrease in cytochrome c oxidase (COX) activity, a decrease in mitochondrial membrane potential and in mitochondrial cytochrome c content. Consequently, we analyzed parameters of oxidative damage and found that AD and MCI cybrids exhibit an increase in lipid peroxides, higher production of superoxide radicals, and higher content in protein carbonyls. Since our data clearly show alterations in mitochondrial-mediated oxidative damage in MCI cybrids we propose that mitochondrial dysfunction is an early event in idiopathic AD. Moreover, we found that mitochondrial Aβ oligomeric content increases in AD, which may exacerbate initial mitochondrial damage. Altogether, our data strongly supports a key role for mitochondria/ mtDNA in aged-driven AD pathology.Export Options
About this article
Cite this article as:
F. Silva D., Santana I., R. Esteves A., Baldeiras I., M. Arduino D., R. Oliveira C. and M. Cardoso S., Prodromal Metabolic Phenotype in MCI Cybrids: Implications for Alzheimer’s Disease, Current Alzheimer Research 2013; 10 (2) . https://dx.doi.org/10.2174/1567205011310020008
DOI https://dx.doi.org/10.2174/1567205011310020008 |
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
-
Heart Failure in Sub-Saharan Africa
Current Cardiology Reviews Conference Report: Summary Report of the International Association of Neurorestoratology VII Conference: Regulations, Ethics, Science, and the Need of Patients Care in Neurorestoratology
CNS & Neurological Disorders - Drug Targets The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia
Current Topics in Medicinal Chemistry Polyphenols as Potential Therapeutics for Pain and Inflammation in Spinal Cord Injury
Current Molecular Pharmacology Conventional and Non-Conventional Targets of Natural Products in the Management of Diabetes Mellitus and Associated Complications
Current Medicinal Chemistry Therapeutic Targeting of the Endoplasmic Reticulum in Alzheimers Disease
Current Alzheimer Research Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction
Current Topics in Medicinal Chemistry Emerging Vascular Risk Factors in Women: Any Differences from Men?
Current Medicinal Chemistry Prospects of Magnetic Resonance Spectroscopy in Mouse Models of Alzheimers Disease
Current Medical Imaging Metal Catalyzed Oxidation of Alpha-Synuclein – A Role for Oligomerization in Pathology?
Current Alzheimer Research Past, Present and Future of Nutrigenomics and its Influence on Drug Development
Current Drug Discovery Technologies Proteoglycans and Glycosaminoglycans in Misfolded Proteins Formation in Alzheimer's Disease
Protein & Peptide Letters Analysis of Univariate and Multivariate Filters Towards the Early Detection of Dementia
Recent Advances in Computer Science and Communications Rosuvastatin, Pravastatin, and Atorvastatin for the Treatment of Hypercholesterolaemia in HIV-Infected Patients Receiving Protease Inhibitors
Current HIV Research A Predictive Model of the Prevalence of Delirium in Elderly Subjects Admitted to Nursing Homes
Endocrine, Metabolic & Immune Disorders - Drug Targets Selegiline (l-Deprenyl) as a Unique Neuroprotective Agent for Chronic Neurodegenerative Disorders- A Lesson from MAO Inhibition
Current Medicinal Chemistry - Central Nervous System Agents Neuroinflammation and Alzheimer's Disease: Implications for Microglial Activation
Current Alzheimer Research Importance of ABC Transporters in Drug Development
Current Pharmaceutical Design Molecular Mechanisms of Ischemic Neuronal Cell Death - With Relevance to Alzheimers Disease
Current Alzheimer Research NMDA Receptor Antagonists as Antidepressant and Antidementia Drugs: Recent Developments and Future Prospects
Current Medicinal Chemistry - Central Nervous System Agents