Abstract
One early and prominent pathologic feature of Alzheimers disease (AD) is the appearance of activated microglia in the vicinity of developing β-amyloid deposits. However, the precise role of microglia during the course of AD is still under discussion. Microglia have been reported to degrade and clear β-amyloid, but they also can exert deleterious effects due to overwhelming inflammatory reactions. Here, we demonstrate the occurrence of developing plaque populations with distinct amounts of associated microglia using time-dependent analyses of plaque morphology and the spatial distribution of microglia in an APP/PS1 mouse model. In addition to a population of larger plaques ( > 700μm2) that are occupied by a moderate contingent of microglial cells across the course of aging, a second type of small β-amyloid deposits develops (≤400μm2) in which the plaque core is enveloped by a relatively large number of microglia. Our analyses indicate that microglia are strongly activated early in the emergence of senile plaques, but that activation is diminished in the later stages of plaque evolution > 150 days). These findings support the view that microglia serve to restrict the growth of senile plaques, and do so in a way that minimizes local inflammatory damage to other components of the brain.
Keywords: Alzheimer's disease, AD, beta-amyloid, neurodegeneration, dementia, microglia, inflammation, immune therapy, blood-brain barrier, phagocytic mechanism, plaque growth, meningoencephalitis, diaminobenzidine
Current Alzheimer Research
Title: Determination of Spatial and Temporal Distribution of Microglia by 230nm-High-Resolution, High-Throughput Automated Analysis Reveals Different Amyloid Plaque Populations in an APP/PS1 Mouse Model of Alzheimers Disease
Volume: 8 Issue: 7
Author(s): Katja Scheffler, Jan Stenzel, Markus Krohn, Cathleen Lange, Jacqueline Hofrichter, Toni Schumacher, Thomas Bruning, Anne-Sophie Plath, Lary Walker and Jens Pahnke
Affiliation:
Keywords: Alzheimer's disease, AD, beta-amyloid, neurodegeneration, dementia, microglia, inflammation, immune therapy, blood-brain barrier, phagocytic mechanism, plaque growth, meningoencephalitis, diaminobenzidine
Abstract: One early and prominent pathologic feature of Alzheimers disease (AD) is the appearance of activated microglia in the vicinity of developing β-amyloid deposits. However, the precise role of microglia during the course of AD is still under discussion. Microglia have been reported to degrade and clear β-amyloid, but they also can exert deleterious effects due to overwhelming inflammatory reactions. Here, we demonstrate the occurrence of developing plaque populations with distinct amounts of associated microglia using time-dependent analyses of plaque morphology and the spatial distribution of microglia in an APP/PS1 mouse model. In addition to a population of larger plaques ( > 700μm2) that are occupied by a moderate contingent of microglial cells across the course of aging, a second type of small β-amyloid deposits develops (≤400μm2) in which the plaque core is enveloped by a relatively large number of microglia. Our analyses indicate that microglia are strongly activated early in the emergence of senile plaques, but that activation is diminished in the later stages of plaque evolution > 150 days). These findings support the view that microglia serve to restrict the growth of senile plaques, and do so in a way that minimizes local inflammatory damage to other components of the brain.
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Scheffler Katja, Stenzel Jan, Krohn Markus, Lange Cathleen, Hofrichter Jacqueline, Schumacher Toni, Bruning Thomas, Plath Anne-Sophie, Walker Lary and Pahnke Jens, Determination of Spatial and Temporal Distribution of Microglia by 230nm-High-Resolution, High-Throughput Automated Analysis Reveals Different Amyloid Plaque Populations in an APP/PS1 Mouse Model of Alzheimers Disease, Current Alzheimer Research 2011; 8 (7) . https://dx.doi.org/10.2174/156720511797633179
DOI https://dx.doi.org/10.2174/156720511797633179 |
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
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