Abstract
The prospects for effectively treating well-established dementia, such as Alzheimer’s disease (AD), are slim, due to the destruction of key brain pathways that underlie higher cognitive function. There has been a substantial shift in the field towards detecting conditions such as AD in their earliest stages, which would allow preventative or therapeutic approaches to substantially reduce risk and/or slow the progression of disease. AD is characterized by hallmark pathological changes such as extracellular Aβ plaques and intracellular neurofibrillary pathology, which selectively affect specific subclasses of neurons and brain circuits. Current evidence indicates that Aβ plaques begin to form many years before overt dementia, a gradual and progressive pathology which offers a potential target for early intervention. Early Aβ changes in the brain result in localized damage to dendrites, axonal processes and synapses, to which excitatory synapses and the processes of projection neurons are highly vulnerable. Aβ pathology is replicated in a range of transgenic models overexpressing mutant human familial AD genes (eg APP and presenilin 1). Studying the development of aberrant regenerative and degenerative changes in neuritic processes associated with Aβ plaques may represent the best opportunity to understand the relationship between the pathological hallmarks of AD and neuronal damage, and to develop early interventions to prevent, slow down or mitigate against Aβ pathology and/or the neuronal alterations that leads to cognitive impairment.
Keywords: Alzheimer’s disease, amyloid precursor protein, Aß, plaque, dystrophic neurite, selective vulnerability, transgenic mice.
Current Alzheimer Research
Title:Defining the earliest pathological changes of Alzheimer’s disease
Volume: 13 Issue: 3
Author(s): James C. Vickers, Stan Mitew, Adele Woodhouse, Carmen M. Fernandez-Martos, Mathew T. Kirkcaldie, Alison J. Canty, Graeme H. McCormack and Anna E. King
Affiliation:
Keywords: Alzheimer’s disease, amyloid precursor protein, Aß, plaque, dystrophic neurite, selective vulnerability, transgenic mice.
Abstract: The prospects for effectively treating well-established dementia, such as Alzheimer’s disease (AD), are slim, due to the destruction of key brain pathways that underlie higher cognitive function. There has been a substantial shift in the field towards detecting conditions such as AD in their earliest stages, which would allow preventative or therapeutic approaches to substantially reduce risk and/or slow the progression of disease. AD is characterized by hallmark pathological changes such as extracellular Aβ plaques and intracellular neurofibrillary pathology, which selectively affect specific subclasses of neurons and brain circuits. Current evidence indicates that Aβ plaques begin to form many years before overt dementia, a gradual and progressive pathology which offers a potential target for early intervention. Early Aβ changes in the brain result in localized damage to dendrites, axonal processes and synapses, to which excitatory synapses and the processes of projection neurons are highly vulnerable. Aβ pathology is replicated in a range of transgenic models overexpressing mutant human familial AD genes (eg APP and presenilin 1). Studying the development of aberrant regenerative and degenerative changes in neuritic processes associated with Aβ plaques may represent the best opportunity to understand the relationship between the pathological hallmarks of AD and neuronal damage, and to develop early interventions to prevent, slow down or mitigate against Aβ pathology and/or the neuronal alterations that leads to cognitive impairment.
Export Options
About this article
Cite this article as:
Vickers C. James, Mitew Stan, Woodhouse Adele, Fernandez-Martos M. Carmen, Kirkcaldie T. Mathew, Canty J. Alison, McCormack H. Graeme and King E. Anna, Defining the earliest pathological changes of Alzheimer’s disease , Current Alzheimer Research 2016; 13 (3) . https://dx.doi.org/10.2174/1567205013666151218150322
DOI https://dx.doi.org/10.2174/1567205013666151218150322 |
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
-
Current Progresses on Nanodelivery Systems for the Treatment of Neuropsychiatric Diseases: Alzheimer’s and Schizophrenia
Current Pharmaceutical Design Thermal Taste and Anti-Aspiration Drugs: A Novel Drug Discovery Against Pneumonia
Current Pharmaceutical Design Development of Small-Molecule Inhibitors of Raf
Recent Patents on Anti-Infective Drug Discovery Current Management and Treatment of Cerebral Vasospasm Complicating SAH
CNS & Neurological Disorders - Drug Targets Antioxidants Suppress Th1-Type Immune Response In Vitro
Drug Metabolism Letters BioArena Studies: Unique Function of Endogenous Formaldehyde and Ozone in the Antibiotic Effect – A Review
Medicinal Chemistry Commentary ( The Renin Angiotensin System in Alzheimers Disease - Do Updates Highlight a Clinical and Biological Dichotomy? )
Current Alzheimer Research Treatment Considerations of Clinical Physician on Hypertension Management in Asia
Current Hypertension Reviews Cholesterol, Copper and Aβ in Controls, MCI, AD and the AD Cholesterol- Lowering Treatment Trial (ADCLT)
Current Alzheimer Research The Panomics Approach in Neurodegenerative Disorders
Current Medicinal Chemistry Diagnosis of Neurodegenerative Diseases: The Clinical Approach
Current Alzheimer Research 2,4,6-Trichlorophenylhydrazine Schiff Bases as DPPH Radical and Super Oxide Anion Scavengers
Medicinal Chemistry Comparison of Changes in Cognitive Functions of Post-stroke Patients with the Computer-based Cognitive Intervention (PABLO System) and Conventional Cognitive Intervention (Paper-pencil Method)
Current Psychiatry Research and Reviews Ginkgolic Acids Confer Potential Anticancer Effects by Targeting Pro- Inflammatory and Oncogenic Signaling Molecules
Current Molecular Pharmacology APOE4 Induces Site-Specific Tau Phosphorylation Through Calpain-CDK5 Signaling Pathway in EFAD-Tg Mice
Current Alzheimer Research Targeting the PAC1 Receptor for Neurological and Metabolic Disorders
Current Topics in Medicinal Chemistry Commentary: Toward a Personalized Medicine in Wake-Up Stroke?
CNS & Neurological Disorders - Drug Targets On the Psychotropic Effects of Carbon Dioxide
Current Pharmaceutical Design A Review of Wavelet Denoising in MRI and Ultrasound Brain Imaging
Current Medical Imaging Alzheimer Disease and Diabetes Mellitus: Do They have Anything in Common?
Current Alzheimer Research