Abstract
The occurrence of a plaque-dependent inflammation in Alzheimers disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in the progression of the AD pathology is still unknown. In this review we discuss the clinical and experimental evidence for the occurrence of inflammation in preclinical, asymptomatic phases of the progression of the AD pathology. In particular, we discuss the evidence from different transgenic models suggesting that a pro-inflammatory process might even be initiated prior to plaque deposition. The factors responsible for the early, pre-plaque inflammation are reviewed, with particular emphasis on the role of soluble Aβ-oligomers. Furthermore, we analyze the consequences of the microglial activation and the deregulation of NGF metabolism, in the context of the earliest amyloid pathology. Finally, we propose MMP-9 as a promising biomarker for signalling early stages of an ongoing CNS inflammation.
Keywords: Preclinical Alzheimer's disease, Aβ oligomers, inflammation, transgenic mice, NGF, MMP-9
Current Alzheimer Research
Title: Does a Pro-Inflammatory Process Precede Alzheimers Disease and Mild Cognitive Impairment?
Volume: 8 Issue: 2
Author(s): M. T. Ferretti and A. C. Cuello
Affiliation:
Keywords: Preclinical Alzheimer's disease, Aβ oligomers, inflammation, transgenic mice, NGF, MMP-9
Abstract: The occurrence of a plaque-dependent inflammation in Alzheimers disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in the progression of the AD pathology is still unknown. In this review we discuss the clinical and experimental evidence for the occurrence of inflammation in preclinical, asymptomatic phases of the progression of the AD pathology. In particular, we discuss the evidence from different transgenic models suggesting that a pro-inflammatory process might even be initiated prior to plaque deposition. The factors responsible for the early, pre-plaque inflammation are reviewed, with particular emphasis on the role of soluble Aβ-oligomers. Furthermore, we analyze the consequences of the microglial activation and the deregulation of NGF metabolism, in the context of the earliest amyloid pathology. Finally, we propose MMP-9 as a promising biomarker for signalling early stages of an ongoing CNS inflammation.
Export Options
About this article
Cite this article as:
T. Ferretti M. and C. Cuello A., Does a Pro-Inflammatory Process Precede Alzheimers Disease and Mild Cognitive Impairment?, Current Alzheimer Research 2011; 8 (2) . https://dx.doi.org/10.2174/156720511795255982
DOI https://dx.doi.org/10.2174/156720511795255982 |
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
-
Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama
Current Aging Science Quantitative Ultrasound in Diagnosis of Metabolic Bone Diseases
Current Medical Imaging Assembly In Vitro of Tau Protein and its Implications in Alzheimers Disease
Current Alzheimer Research Immune Functions of Glia and Neurons in the Central Nervous System
Current Immunology Reviews (Discontinued) Identification of High-affinity Small Molecules Targeting Gamma Secretase for the Treatment of Alzheimer’s Disease
Current Topics in Medicinal Chemistry Pros and Cons of Medical Cannabis use by People with Chronic Brain Disorders
Current Neuropharmacology Possible Molecular Interactions of Bexarotene - A Retinoid Drug and Alzheimer's Aβ Peptide: A Docking Study
Current Alzheimer Research Conformations and Biological Activities of Amyloid Beta Peptide 25-35
Current Protein & Peptide Science Virus Vasculopathy and Stroke: An Under-Recognized Cause and Treatment Target
Infectious Disorders - Drug Targets Recent Advances in Transcranial Focused Ultrasound (FUS) Triggered Brain Delivery
Current Drug Targets Association of Mean Platelet Volume with Hypertension in Rheumatoid Arthritis
Inflammation & Allergy - Drug Targets (Discontinued) Pharmacological Investigation and Unraveling Mechanism of Action of Jasminum sambac Flowers for Predicated Treatment of Alzheimer’s Disease
Current Nutrition & Food Science Anticholinesterase and Antioxidant Activities of Natural Abietane Diterpenoids with Molecular Docking Studies
Current Alzheimer Research Endocannabinoid System in Neurological Disorders
Recent Patents on CNS Drug Discovery (Discontinued) The Endocannabinoid System and Schizophrenia: Integration of Evidence
Current Pharmaceutical Design Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: A Review
Current Drug Therapy Meet Our Editorial Board Member
Current Alzheimer Research Effect of Polyherbal Drug Majun Falasfa on the Transgenic Drosophila Model of Parkinson’s Disease
Current Traditional Medicine Recent Progress in the Medicinal Chemistry of γ-Secretase Inhibitors
Current Topics in Medicinal Chemistry Induced Adaptive Resistance to Nitrooxidative Stress in the CNS: Therapeutic Implications
Central Nervous System Agents in Medicinal Chemistry