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.
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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
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
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