Abstract
The drawbacks of amyloid immunotherapy, including the development of encephalitis, the lack of clinical improvement and of any effect on neurofibrillary tangles (NFTs), coupled with the central role of NFTs in dementia, may point that clearance of amyloid pathology is not sufficient for improving the dementia symptoms in Alzheimer’s disease (AD) patients. This further supported the concept that immunotherapy targeting the NFT proteinous aggregates may be preferential. Yet, the encephalitogenicity of full-length tau protein under a proinflammatory CNS milieu, reported by us in immunized mice, demands to carefully and selectively target pathological tau, while not the normal functional tau, and assuring both efficacy (anti-NFT effect) as well as safety (free of encephalitis) of a potential vaccine. Accumulating evidence from animal studies shows that tau-immunotherapy, targeting selectively pathological tau, particularly the phosphorylated- tau isoforms, reduces the tau-pathology and improves the symptoms of dementia. These findings are based on studies from different research groups, including our laboratory, conducted in different animal models and using various immunization protocols. There is also evidence that the decrease in NFTs is antibody-mediated involving the endosomal/ lysosomal pathway. No adverse effects were reported by the research groups, including also our study in which mice were immunized with a single injection of phosphorylated-tau peptide under a CNS proinflammatory milieu. In this review, I discuss the studies reported in this field, focusing on different approaches, different immunization protocols and mechanistic aspects, with a focus on the promising efficacy of the tau-immunotherapy, while addressing the safety issues already in the preclinical stage, before progressing to clinical trials.
Keywords: Tau, neurofibrillary-tangles, tauopathy, immunotherapy, efficacy, safety
Current Alzheimer Research
Title:Immunotherapy for Targeting Tau Pathology in Alzheimer’s Disease and Tauopathies
Volume: 10 Issue: 3
Author(s): Hanna Rosenmann
Affiliation:
Keywords: Tau, neurofibrillary-tangles, tauopathy, immunotherapy, efficacy, safety
Abstract: The drawbacks of amyloid immunotherapy, including the development of encephalitis, the lack of clinical improvement and of any effect on neurofibrillary tangles (NFTs), coupled with the central role of NFTs in dementia, may point that clearance of amyloid pathology is not sufficient for improving the dementia symptoms in Alzheimer’s disease (AD) patients. This further supported the concept that immunotherapy targeting the NFT proteinous aggregates may be preferential. Yet, the encephalitogenicity of full-length tau protein under a proinflammatory CNS milieu, reported by us in immunized mice, demands to carefully and selectively target pathological tau, while not the normal functional tau, and assuring both efficacy (anti-NFT effect) as well as safety (free of encephalitis) of a potential vaccine. Accumulating evidence from animal studies shows that tau-immunotherapy, targeting selectively pathological tau, particularly the phosphorylated- tau isoforms, reduces the tau-pathology and improves the symptoms of dementia. These findings are based on studies from different research groups, including our laboratory, conducted in different animal models and using various immunization protocols. There is also evidence that the decrease in NFTs is antibody-mediated involving the endosomal/ lysosomal pathway. No adverse effects were reported by the research groups, including also our study in which mice were immunized with a single injection of phosphorylated-tau peptide under a CNS proinflammatory milieu. In this review, I discuss the studies reported in this field, focusing on different approaches, different immunization protocols and mechanistic aspects, with a focus on the promising efficacy of the tau-immunotherapy, while addressing the safety issues already in the preclinical stage, before progressing to clinical trials.
Export Options
About this article
Cite this article as:
Rosenmann Hanna, Immunotherapy for Targeting Tau Pathology in Alzheimer’s Disease and Tauopathies, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030001
DOI https://dx.doi.org/10.2174/1567205011310030001 |
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
-
Recent Patents on Alphavirus Protein Expression and Vector Production
Recent Patents on Biotechnology Dengue Fever: Theories of Immunopathogenesis and Challenges for Vaccination
Inflammation & Allergy - Drug Targets (Discontinued) Regulation of Apoptosis by Gram-Positive Bacteria: Mechanistic Diversity and Consequences for Immunity
Current Immunology Reviews (Discontinued) Is Helicobacter pylori the Infectious Trigger for Headache?: A Review
Infectious Disorders - Drug Targets The Role of α7 Nicotinic Acetylcholine Receptors and α7-Specific Antibodies in Neuroinflammation Related to Alzheimer Disease
Current Pharmaceutical Design The Role of Extracellular Adenosine in Chemical Neurotransmission in the Hippocampus and Basal Ganglia: Pharmacological and Clinical Aspects
Current Topics in Medicinal Chemistry An Insight into the Dermatological Applications of Neem: A Review on Traditional and Modern Aspect
Recent Advances in Anti-Infective Drug Discovery Bridge Between Neuroimmunity and Traumatic Brain Injury
Current Pharmaceutical Design Astrocyte Infection by HIV-1: Mechanisms of Restricted Virus Replication, and Role in the Pathogenesis of HIV-1-Associated Dementia
Current HIV Research Mechanisms of HIV-1 Tat Neurotoxicity via CDK5 Translocation and Hyper-Activation: Role in HIV-Associated Neurocognitive Disorders
Current HIV Research Membrane Interacting Peptides: A Review
Current Protein & Peptide Science Capacity Building in Genomics Medicine and Molecular Diagnostics: The Case of Sri Lanka
Current Pharmacogenomics and Personalized Medicine The Yin and Yang of Antiviral Innate Immunity in Central Nervous System
Current Pharmaceutical Design Delivery of Anti-Viral Nucleoside Analogues to the Central Nervous System
Current Medicinal Chemistry - Anti-Infective Agents mGluRI Targets Microglial Activation and Selectively Prevents Neuronal Cell Engulfment Through Akt and Caspase Dependent Pathways
Current Neurovascular Research Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future
Current Drug Metabolism Recent Patents in CNS Drug Discovery: The Management of Inflammation in the Central Nervous System
Recent Patents on CNS Drug Discovery (Discontinued) Inflammation and Immunology of the Vitreoretinal Compartment
Inflammation & Allergy - Drug Targets (Discontinued) Safe and Effective Delivery of Amphotericin B: A Survey of Patents
Recent Patents on Nanotechnology Using Biologic Agents in Pediatric Rheumatologic Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry