Abstract
Fibrillar aggregates of abnormally hyperphosphorylated tau protein are the major component of the pathological entities, including intraneuronal neurofibrillary tangles that define the broad class of late-onset neurodegenerative disorders called the tauopathies. Mutations in the tau gene (MAPT) causing familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) confirm that tau protein dysfunction could be a primary cause of neuronal loss. However, in the sporadic tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) where MAPT mutation is absent, common variation in MAPT that defines the H1 and H2 haplotype clades strongly influences disease risk. Surprisingly, this influence on risk extends to sporadic Parkinsons disease (PD), traditionally not defined as a tauopathy. This review will focus on recent work aimed at elucidating the mechanistic basis of this haplotypespecific effect on disease risk, implicating elevated levels of MAPT expression, particularly via increased transcription and/or alterations in splicing. This conforms to an emerging picture of a shared mechanism that underlies the fundamental process(es) leading to neuronal death. Increased availability of the fibrillogenic protein substrates of the pathological aggregates that define several neurodegenerative proteopathies, eg α-synuclein in PD, β-amyloid in AD and tau in the tauopathies, contributes to causation and risk in the familial and sporadic forms of these disorders, respectively.
Keywords: Tau, tauopathy, alzheimer, parkinsonism, genetics, progressive supranuclear palsy.
Current Alzheimer Research
Title: Disentangling the Role of the Tau Gene Locus in Sporadic Tauopathies
Volume: 7 Issue: 8
Author(s): J. Vandrovcova, F. Anaya, V. Kay, A. Lees, J. Hardy and R. de Silva
Affiliation:
Keywords: Tau, tauopathy, alzheimer, parkinsonism, genetics, progressive supranuclear palsy.
Abstract: Fibrillar aggregates of abnormally hyperphosphorylated tau protein are the major component of the pathological entities, including intraneuronal neurofibrillary tangles that define the broad class of late-onset neurodegenerative disorders called the tauopathies. Mutations in the tau gene (MAPT) causing familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) confirm that tau protein dysfunction could be a primary cause of neuronal loss. However, in the sporadic tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) where MAPT mutation is absent, common variation in MAPT that defines the H1 and H2 haplotype clades strongly influences disease risk. Surprisingly, this influence on risk extends to sporadic Parkinsons disease (PD), traditionally not defined as a tauopathy. This review will focus on recent work aimed at elucidating the mechanistic basis of this haplotypespecific effect on disease risk, implicating elevated levels of MAPT expression, particularly via increased transcription and/or alterations in splicing. This conforms to an emerging picture of a shared mechanism that underlies the fundamental process(es) leading to neuronal death. Increased availability of the fibrillogenic protein substrates of the pathological aggregates that define several neurodegenerative proteopathies, eg α-synuclein in PD, β-amyloid in AD and tau in the tauopathies, contributes to causation and risk in the familial and sporadic forms of these disorders, respectively.
Export Options
About this article
Cite this article as:
Vandrovcova J., Anaya F., Kay V., Lees A., Hardy J. and de Silva R., Disentangling the Role of the Tau Gene Locus in Sporadic Tauopathies, Current Alzheimer Research 2010; 7 (8) . https://dx.doi.org/10.2174/156720510793611619
DOI https://dx.doi.org/10.2174/156720510793611619 |
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
-
Cerebral White Matter Lesions, Risk of Stroke and Cerebrovascular Protection with Angiotensin Receptor Blockers
Current Drug Therapy Identifying Patterns in Signs and Symptoms Preceding the Clinical Diagnosis of Alzheimer’s Disease: Retrospective Medical Record Review Study and a Nested Case-control Design
Current Alzheimer Research An Update on New Cholesterol Inhibitor: Bempedoic Acid
Current Cardiology Reviews Editorial: (Thematic Issue) Novel Concepts on the Blood-Brain Barrier and Brain Pathology. New Therapeutic Approaches
CNS & Neurological Disorders - Drug Targets Current Clinical Applications of Botulinum Toxin
Current Pharmaceutical Design Potential Therapeutic Effects of Exogenous Ketone Supplementation for Type 2 Diabetes: A Review
Current Pharmaceutical Design AD Vaccines: Conclusions and Future Directions
CNS & Neurological Disorders - Drug Targets The Glutathione System and its Regulation by Neurohormone Melatonin in the Central Nervous System
Central Nervous System Agents in Medicinal Chemistry Methylated MicroRNA Genes of the Developing Murine Palate
MicroRNA Diffusion Tensor Imaging in Alzheimers Disease
Current Medical Imaging A Novel Relationship for Schizophrenia, Bipolar and Major Depressive Disorder Part 6: A Hint from Chromosome 6 High Density Association Screen
Current Molecular Medicine Folate-modified Graphene Oxide as the Drug Delivery System to Load Temozolomide
Current Pharmaceutical Biotechnology Tools in the Design of Therapeutic Drugs for CNS Disorders: An up-to-date Review
Current Molecular Pharmacology Hyponatraemia Associated with Trimethoprim Use
Current Drug Safety Atrial Remodeling and Novel Pharmacological Strategies for Antiarrhythmic Therapy in Atrial Fibrillation
Current Medicinal Chemistry Role of Opioid Antagonists in the Treatment of Women with Glucoregulation Abnormalities
Current Pharmaceutical Design The Role of Annexin A1 and Formyl Peptide Receptor 2/3 Signaling in Chronic Corticosterone-Induced Depression-Like behaviors and Impairment in Hippocampal-Dependent Memory
CNS & Neurological Disorders - Drug Targets Rapid Improvement of Canine Cognitive Dysfunction with Immunotherapy designed for Alzheimer's Disease
Current Alzheimer Research A Nanotechnological Approach to the Management of Alzheimer Disease and Type 2 Diabetes
CNS & Neurological Disorders - Drug Targets Brain Derived Neurotrophic Factor and Cognitive Status: The Delicate Balance Among People Living with HIV, with and without Alcohol Abuse
Current HIV Research