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Inflammatory response in Alzheimer's disease
1Division of Neuropathology, Tokyo Institute of Psychiatry, Japan.
Abstract:
Microglia belong to the mononuclear phagocyte system. They represent the brain resident tissue macrophages and function as the scavenger cells in brain. In Alzheimer's disease (AD), microglia become activated. Reactive microglia aggregate around senile plaque beta-amyloid and neurofibrillary tangles. Heavy accumulation of these pathological debris in postmortem, however, indicates the failure or, at best, partial success of the removal. It is supposed that continued activation of microglia in these lesions elicits a persistent inflammatory response. In fact, activation fragments of the complement system have been detected in association with beta-amyloid deposits and extracellular ghost tangles. Thrombin, a central serine protease of the coagulation pathway, is also deposited in these pathological debris. Both complements and thrombin could augment the biochemical, synthetic and phagocytic capacities of microglia. Microglia, in turn, might play a major role for the activation of complement and coagulation systems in brain. The available evidence strongly suggests a significant similarity between the chronic inflammation and the tissue response in AD lesions, supporting a notion that the inflammatory process is a part of Alzheimer pathology.
Insights
Microglia, the brain's scavenger cells, become activated in Alzheimer's disease (AD). Their persistent activation and inflammatory response contribute to AD pathology, despite attempts to clear debris.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia are the brain's resident macrophages, acting as scavenger cells.
- In Alzheimer's disease (AD), microglia become activated and aggregate around pathological hallmarks like beta-amyloid plaques and neurofibrillary tangles.
- The accumulation of debris suggests limited efficacy of microglial clearance in AD.
Purpose of the Study:
- To investigate the role of microglia activation and associated inflammatory responses in Alzheimer's disease pathology.
- To explore the interplay between microglia, complement system, and coagulation pathways in the context of AD.
- To determine if chronic inflammation is an integral component of Alzheimer's disease.
Main Methods:
- Analysis of postmortem brain tissue from Alzheimer's disease patients.
- Detection of activated microglia, beta-amyloid deposits, and neurofibrillary tangles.
- Assessment of complement system activation fragments and thrombin deposition.
Main Results:
- Reactive microglia accumulate around senile plaques and neurofibrillary tangles in AD brains.
- Activation fragments of the complement system and thrombin are found associated with pathological debris.
- Evidence suggests that complement and thrombin can enhance microglial functions.
- Microglia may contribute to the activation of complement and coagulation systems within the brain.
Conclusions:
- The persistent inflammatory response mediated by activated microglia is a significant feature of Alzheimer's disease pathology.
- The interaction between microglia, complement, and coagulation systems likely plays a crucial role in AD pathogenesis.
- Chronic inflammation is strongly implicated as a component of Alzheimer's disease.