Abstract
Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS. As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that are age-appropriate to delay AD in DS.
Keywords: Beta-amyloid, neurofibrillary tangles, neuroinflammation, oxidative damage, posttranslational modifications, senile plaques, trisomy 21, vascular pathology, white matter damage.
Current Alzheimer Research
Title:Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology
Volume: 13 Issue: 1
Author(s): Elizabeth Head, Ira T. Lott, Donna M. Wilcock and Cynthia A. Lemere
Affiliation:
Keywords: Beta-amyloid, neurofibrillary tangles, neuroinflammation, oxidative damage, posttranslational modifications, senile plaques, trisomy 21, vascular pathology, white matter damage.
Abstract: Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS. As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that are age-appropriate to delay AD in DS.
Export Options
About this article
Cite this article as:
Head Elizabeth, T. Lott Ira, M. Wilcock Donna and A. Lemere Cynthia, Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology, Current Alzheimer Research 2016; 13 (1) . https://dx.doi.org/10.2174/1567205012666151020114607
DOI https://dx.doi.org/10.2174/1567205012666151020114607 |
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
-
Neuroprotection Abilities of Cytosolic Phospholipase A2 Inhibitors in Kainic acid-induced Neurodegeneration
Current Drug Targets - Cardiovascular & Hematological Disorders ADAM10 as a Therapeutic Target for Cancer and Inflammation
Current Pharmaceutical Design Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets
CNS & Neurological Disorders - Drug Targets MicroRNA Landscape in Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets The Effects of Lipid-Regulating Therapy on Haemostatic Parameters
Current Pharmaceutical Design Filling the Gaps in the Aβ Cascade Hypothesis of Alzheimers Disease
Current Alzheimer Research Chondroitin Sulfate, a Major Niche Substance of Neural Stem Cells, and Cell Transplantation Therapy of Neurodegeneration Combined with Niche Modification
Current Stem Cell Research & Therapy Psychobiological Model of Personality: Guidelines for Pharmacotherapy of Personality Disorder
Current Psychopharmacology A Surgical Opinion on Hyperalgesia/Nociception, Inflammatory/Neurogenic Pain and Anti-inflammatory Responses and Drug Interventions Revisited: Current Breakthroughs and Views
Current Immunology Reviews (Discontinued) Effect of Aging on Metabolic Pathways in Endothelial Progenitor Cells
Current Pharmaceutical Design Extracellular Citrate in Health and Disease
Current Molecular Medicine New Trends in the Design of Drugs Against Alzheimers Disease
Current Medicinal Chemistry Data-driven Approach to Detect and Predict Adverse Drug Reactions
Current Pharmaceutical Design Possible Neuroprotective Strategies for Huntingtons Disease
Current Neuropharmacology Self-Emulsifying Drug Delivery Systems: Strategy for Improving Oral Delivery of Poorly Soluble Drugs
Current Drug Therapy Pharmacotherapy for Late-Life Depression with Psychotic Features: A Review of Literature of Randomized Control Trials
Current Psychiatry Reviews Post-stroke Depression Therapy: Where are we now?
Current Neurovascular Research The Human Leukocyte Antigen Class III Haplotype Approach: New Insight in Alzheimer's Disease Inflammation Hypothesis
Current Alzheimer Research Nutraceuticals and "Repurposed" Drugs of Phytochemical Origin in Prevention and Interception of Chronic Degenerative Diseases and Cancer
Current Medicinal Chemistry Applications of Arterial Spin Labelling in Mild Cognitive Impairment, Alzheimers Disease and Other Forms of Dementia
Current Medical Imaging