Abstract
Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Aβ) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Aβ may directly or indirectly interact with tau to accelerate NFT formation. Here we review recent evidence that Aβ can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mis-localization, and accumulation. Studies are presented that support four putative mechanisms by which Aβ may facilitate the development of tau pathology. A great deal of work suggests that Aβ may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Aβ may enhance tau hyperphosphorylation and NFT formation. In the AD brain, Aβ also triggers a massive inflammatory response and pro-inflammatory cytokines can in turn indirectly modulate tau phosphorylation. Mounting evidence also suggests that Aβ may inhibit tau degradation via the proteasome. Lastly, Aβ and tau may indirectly interact at the level of axonal transport and evidence is presented for two possible scenarios by which axonal transport deficits may play a role. We propose that the four putative mechanisms described in this review likely mediate the interactions between Aβ and tau, thereby leading to the development of AD neurodegeneration.
Keywords: Phosphorylation, inflammation, proteasome, axonal transport, neurofibrillary tangles, PHF, oligomer, amyloid
Current Alzheimer Research
Title: Pathways by Which Aβ Facilitates Tau Pathology
Volume: 3 Issue: 5
Author(s): Mathew Blurton-Jones and Frank M. LaFerla
Affiliation:
Keywords: Phosphorylation, inflammation, proteasome, axonal transport, neurofibrillary tangles, PHF, oligomer, amyloid
Abstract: Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Aβ) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Aβ may directly or indirectly interact with tau to accelerate NFT formation. Here we review recent evidence that Aβ can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mis-localization, and accumulation. Studies are presented that support four putative mechanisms by which Aβ may facilitate the development of tau pathology. A great deal of work suggests that Aβ may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Aβ may enhance tau hyperphosphorylation and NFT formation. In the AD brain, Aβ also triggers a massive inflammatory response and pro-inflammatory cytokines can in turn indirectly modulate tau phosphorylation. Mounting evidence also suggests that Aβ may inhibit tau degradation via the proteasome. Lastly, Aβ and tau may indirectly interact at the level of axonal transport and evidence is presented for two possible scenarios by which axonal transport deficits may play a role. We propose that the four putative mechanisms described in this review likely mediate the interactions between Aβ and tau, thereby leading to the development of AD neurodegeneration.
Export Options
About this article
Cite this article as:
Blurton-Jones Mathew and LaFerla M. Frank, Pathways by Which Aβ Facilitates Tau Pathology, Current Alzheimer Research 2006; 3 (5) . https://dx.doi.org/10.2174/156720506779025242
DOI https://dx.doi.org/10.2174/156720506779025242 |
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
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...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
- 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
-
Cognition in Non-Demented Diabetic Older Adults
Current Aging Science Targeting Nicotinic Receptors for Parkinson's Disease Therapy
CNS & Neurological Disorders - Drug Targets Effect of Simvastatin on Inflammatory Cytokines Balance in Air Pouch Granuloma Model
Inflammation & Allergy - Drug Targets (Discontinued) A High Accumulation of Hair Minerals in Mongolian People: 2nd Report; Influence of Manganese, Iron, Lead, Cadmium and Aluminum to Oxidative Stress, Parkinsonism and Arthritis
Current Aging Science Tetrahydrobiopterin Pathway may Provide Novel Molecular Targets for Acute and Long Term Efficacy of Mood-Regulating Drugs
Current Pharmacogenomics and Personalized Medicine Lipid Lowering Therapy in the Elderly: Is there a Benefit?
Current Pharmaceutical Design Cardiac Effect of Cholinesterase Inhibitors Used in Alzheimers Disease - from Basic Research to Bedside
Current Alzheimer Research Antithrombotic Therapy in Cardiac Embolism
Current Cardiology Reviews Structure-Function Implications in Alzheimers Disease: Effect of Aβ Oligomers at Central Synapses
Current Alzheimer Research Management and Treatment of Cardiovascular Diseases in the Elderly
Current Pharmacogenomics and Personalized Medicine Hypersexuality As a Neuropsychiatric Disorder: The Neurobiology and Treatment Options
Current Drug Targets NADPH Oxidases and Inflammatory Bowel Disease
Current Medicinal Chemistry Recent Developments in Cholinesterases Inhibitors for Alzheimers Disease Treatment
Current Medicinal Chemistry Effects of Gene and Plasma Tau on Cognitive Impairment in Rural Chinese Population
Current Alzheimer Research Donepezil May Reduce Insulin-Like Growth Factor-1 (IGF-1) Levels in Alzheimer’s disease
CNS & Neurological Disorders - Drug Targets Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure
Current Pharmaceutical Design Alzheimer's Disease and Diabetes: New Insights and Unifying Therapies
Current Diabetes Reviews Editorial- Update on Current Alzheimer Research
Current Alzheimer Research Going up in Smoke? A Review of nAChRs-based Treatment Strategies for Improving Cognition in Schizophrenia
Current Pharmaceutical Design Importance of P-gp PET Imaging in Pharmacology
Current Pharmaceutical Design