Abstract
Late onset Alzheimer’s disease (LOAD) is a non-familial, progressive neurodegenerative disease and the most prominent form of dementia in the elderly. Accumulating evidence suggests that LOAD not only results from the combined effects of variation in a number of genes and environmental factors, but also from epigenetic abnormalities such as histone modifications or DNA methylation. In comparison to monogenic diseases, LOAD exhibits numerous anomalies that suggest an epigenetic component in disease etiology. Evidence against a monogenic course and for an epigenetic component include: 1) the dominance of sporadic cases over familial ones and the low estimated concordance rates for monozygotic twins; 2) gender specific susceptibility and course of disease; 3) parent–of–origin effects, and late age of onset; 4) brain chromatin abnormalities, non–Mendelian inheritance patterns, and atypical levels of folate and homocysteine; and 5) monoallelic expression patterns of susceptibility genes [1]. The epigenome is particularly susceptible to deregulation during early embryonic and neonatal periods and thus disturbances during these periods can have latent lasting effects. The Latent Early-life Associated Regulation (LEARn) model attempts to explain these consequences from a brain specific point of view. In the present review we present the evidence that support the role of epigenetics in the development of AD and explore the potential pathways and mechanisms that may be involved.
Keywords: Alzheimer’s disease, cognitive function, amyloid hypothesis, APP, LOAD.
Current Alzheimer Research
Title:Do Epigenetic Pathways Initiate Late Onset Alzheimer Disease (LOAD): Towards a New Paradigm
Volume: 9 Issue: 5
Author(s): Syed Waseem Bihaqi, Axel Schumacher, Bryan Maloney, Debomoy K. Lahiri and Nasser H. Zawia
Affiliation:
Keywords: Alzheimer’s disease, cognitive function, amyloid hypothesis, APP, LOAD.
Abstract: Late onset Alzheimer’s disease (LOAD) is a non-familial, progressive neurodegenerative disease and the most prominent form of dementia in the elderly. Accumulating evidence suggests that LOAD not only results from the combined effects of variation in a number of genes and environmental factors, but also from epigenetic abnormalities such as histone modifications or DNA methylation. In comparison to monogenic diseases, LOAD exhibits numerous anomalies that suggest an epigenetic component in disease etiology. Evidence against a monogenic course and for an epigenetic component include: 1) the dominance of sporadic cases over familial ones and the low estimated concordance rates for monozygotic twins; 2) gender specific susceptibility and course of disease; 3) parent–of–origin effects, and late age of onset; 4) brain chromatin abnormalities, non–Mendelian inheritance patterns, and atypical levels of folate and homocysteine; and 5) monoallelic expression patterns of susceptibility genes [1]. The epigenome is particularly susceptible to deregulation during early embryonic and neonatal periods and thus disturbances during these periods can have latent lasting effects. The Latent Early-life Associated Regulation (LEARn) model attempts to explain these consequences from a brain specific point of view. In the present review we present the evidence that support the role of epigenetics in the development of AD and explore the potential pathways and mechanisms that may be involved.
Export Options
About this article
Cite this article as:
Waseem Bihaqi Syed, Schumacher Axel, Maloney Bryan, K. Lahiri Debomoy and H. Zawia Nasser, Do Epigenetic Pathways Initiate Late Onset Alzheimer Disease (LOAD): Towards a New Paradigm, Current Alzheimer Research 2012; 9 (5) . https://dx.doi.org/10.2174/156720512800617982
DOI https://dx.doi.org/10.2174/156720512800617982 |
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
-
Anti-Cancer Drugs Targeting Fatty Acid Synthase (FAS)
Recent Patents on Anti-Cancer Drug Discovery The Therapeutic Potential of Induced Pluripotent Stem Cells After Stroke: Evidence from Rodent Models
Current Stem Cell Research & Therapy The Role of Vascular Cell Senescence in Atherosclerosis: Antisenescence as a Novel Therapeutic Strategy for Vascular Aging
Current Vascular Pharmacology The Role of Angiotensin Type 1 Receptor in Inflammation and Endothelial Dysfunction
Recent Patents on Cardiovascular Drug Discovery Stem Cells as In Vitro Models of Disease
Current Stem Cell Research & Therapy Recent Patents on Live Bacteria and their Products as Potential Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Prognostic Role of miRNAs in Coronary Artery Disease
Current Topics in Medicinal Chemistry How Recent Patents Have Changed our Clinical Approach in Cardio-Thoracic Surgery
Recent Patents on Regenerative Medicine Recent Patents on Blueberry Picking
Recent Patents on Mechanical Engineering Role of Endogenous Androgen Against Insulin Resistance and Athero-sclerosis in Men with Type 2 Diabetes
Current Diabetes Reviews PCSK9 Inhibition - A Novel Mechanism to Treat Lipid Disorders?
Current Pharmaceutical Design Aldosterone and the Pathogenesis of Hypertension
Current Hypertension Reviews Impact of 13Valent Vaccine for Prevention of Pneumococcal Diseases in Children and Adults at Risk: Possible Scenarios in Campania Region
Infectious Disorders - Drug Targets A Review on Natural Sources Derived Protein Nanoparticles as Anticancer Agents
Current Topics in Medicinal Chemistry Computer-Aided Detection (CADe) System for Detection of Malignant Lung Nodules in CT Slices - a Key for Early Lung Cancer Detection
Current Medical Imaging Genes, Environment, Intermediate Phenotypes, and the Pathogenesis of Diabetic Nephropathy
Current Pharmacogenomics MicroRNAs: A Critical Regulator and a Promising Therapeutic and Diagnostic Molecule for Diabetic Cardiomyopathy
Current Gene Therapy Inorganic Nanoparticles for In Vitro Cancer Diagnosis: A Patent Review
Recent Patents on Nanomedicine An Update on “Selenium Containing Compounds from Poison to Drug Candidates: A Review on the GPx-like Activity”
Current Chemical Biology UKPDS Risk Engine, Decode and Diabetes PHD Models for the Estimation of Cardiovascular Risk in Patients with Diabetes
Current Diabetes Reviews