Abstract
Alzheimer's disease is a progressive neurodegenerative illness characterized by the invariant existence of β-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Aβ cascade has questioned the causal role of this pathway. There is a growing appreciation that the pathogenesis of the illness is multifactorial with Amyloid Beta, Phosphorylated Tau (ptau), inflammation, mitochondrial dysfunction, calcium dyshomeostasis, heavy metal imbalances, and GSK-3 interact in a highly complex manner to provoke a selfsustaining spiraling cascade of pathology, driving disease progression. In the light of such complex pathology, the failure of drugs aimed a targeting single molecules is not surprising as such approaches are usually ineffective against other complex diseases with a multifactorial pathogenesis. Combination therapies or multi target drugs might be more effective in controlling such illnesses. The putative neuroprotective effects of Lithium are achieved via the positive modulation of numerous homeostatic mechanisms regulating autophagy, oxidative stress, inflammation, and mitochondrial dysfunction likely achieved by inhibiting GSK-3 and inositol-145 triphosphate. Data regarding efficacy in human trials and animal models of AD are mixed, but recent data using “microdose” lithium in mild cognitive impairment is encouraging, hence lithium could be a putative multi target treatment in these patients. However, additional well designed long-term trials are needed to confirm its efficacy and safety, given that long term use is necessary to achieve reasonable therapeutic benefit.
Keywords: Alzheimer’s disease, amyloid, beta tau, calcium, dementia, inflammation, iron, lithium, microglia, mitochondria, oxidative stress, phosphorylation.
Current Alzheimer Research
Title:The Putative Use of Lithium in Alzheimer’s Disease
Volume: 13 Issue: 8
Author(s): Gerwyn Morris and Michael Berk
Affiliation:
Keywords: Alzheimer’s disease, amyloid, beta tau, calcium, dementia, inflammation, iron, lithium, microglia, mitochondria, oxidative stress, phosphorylation.
Abstract: Alzheimer's disease is a progressive neurodegenerative illness characterized by the invariant existence of β-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Aβ cascade has questioned the causal role of this pathway. There is a growing appreciation that the pathogenesis of the illness is multifactorial with Amyloid Beta, Phosphorylated Tau (ptau), inflammation, mitochondrial dysfunction, calcium dyshomeostasis, heavy metal imbalances, and GSK-3 interact in a highly complex manner to provoke a selfsustaining spiraling cascade of pathology, driving disease progression. In the light of such complex pathology, the failure of drugs aimed a targeting single molecules is not surprising as such approaches are usually ineffective against other complex diseases with a multifactorial pathogenesis. Combination therapies or multi target drugs might be more effective in controlling such illnesses. The putative neuroprotective effects of Lithium are achieved via the positive modulation of numerous homeostatic mechanisms regulating autophagy, oxidative stress, inflammation, and mitochondrial dysfunction likely achieved by inhibiting GSK-3 and inositol-145 triphosphate. Data regarding efficacy in human trials and animal models of AD are mixed, but recent data using “microdose” lithium in mild cognitive impairment is encouraging, hence lithium could be a putative multi target treatment in these patients. However, additional well designed long-term trials are needed to confirm its efficacy and safety, given that long term use is necessary to achieve reasonable therapeutic benefit.
Export Options
About this article
Cite this article as:
Morris Gerwyn and Berk Michael, The Putative Use of Lithium in Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (8) . https://dx.doi.org/10.2174/1567205013666160219113112
DOI https://dx.doi.org/10.2174/1567205013666160219113112 |
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
-
Cannabinoids and Neuro-Inflammation: Regulation of Brain Immune Response
Recent Patents on CNS Drug Discovery (Discontinued) Platelets and Platelet Interaction with Progenitor Cells in Vascular Homeostasis and Inflammation
Current Vascular Pharmacology Biologics and the Cardiovascular System: A Double-Edged Sword
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Performance Evaluation in Medical Image Segmentation
Current Medical Imaging Molecular and Cellular Mechanisms for Alzheimers Disease:Understanding APP Metabolism
Current Molecular Medicine Stressing Out Hsp90 in Neurotoxic Proteinopathies
Current Topics in Medicinal Chemistry Bupropion HCL and Sleep in Patients with Depression
Current Psychiatry Reviews Can Non-invasive Biomarkers Lead to an Earlier Diagnosis of Alzheimer’s Disease?
Current Alzheimer Research A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials
Current Alzheimer Research Modifiable Risk Factors for Dementia: The Role of Gut Microbiota
Current Alzheimer Research Biomarkers of Protein Oxidation in Human Disease
Current Molecular Medicine Cognitive Impairment Associated with Parkinson’s Disease: Role of Mitochondria
Current Neuropharmacology The Effect of Cognitive Remediation Therapy on Social Skills in Institutionalized Elderly Patients with Schizophrenia
Reviews on Recent Clinical Trials Role of DAP12 in Innate and Adaptive Immune Responses
Current Pharmaceutical Design Current Role and Future Perspectives of Radioiodinated MIBG in the Evaluation of Dementia with Lewy Bodies
Current Radiopharmaceuticals An Historical Perspective on Efforts to Treat Transmissible Spongiform Encephalopathy
CNS & Neurological Disorders - Drug Targets Adenosine in the Central Nervous System: Effects on Neurotransmission and Neuroprotection
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Multicenter Randomized Controlled Trial for the Treatment of Ulcerative Colitis with a Leukocytapheresis Column
Current Pharmaceutical Design An Insight into Codon Pattern Analysis of Autophagy Genes Associated with Virus Infection
Current Pharmaceutical Design Epigenetic Drugs in Cognitive Disorders
Current Pharmaceutical Design