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Microglia in degenerative neurological disease
P L McGeer1, T Kawamata, D G Walker
1Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada.
Glia
|January 1, 1993
Summary
Microglia in chronic neurological diseases like Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) express immune cell markers. This suggests a role for immune responses and self-destruction in neurodegeneration.
Area of Science:
- Neuroimmunology
- Neurodegenerative Diseases
- Cellular Biology
Background:
- Microglia, the brain's resident immune cells, express leukocyte surface antigens, which are elevated in chronic neurodegenerative conditions such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS).
- These upregulated antigens include leukocyte common antigen, immunoglobulin Fc receptors, MHC class I and II glycoproteins, beta 2-integrins, and the vitronectin receptor.
- Ligands for these receptors, including immunoglobulins, complement proteins, T lymphocytes, and vitronectin, are also present in the brain, with some T cells infiltrating neural tissue.
Purpose of the Study:
- To investigate the expression of leukocyte surface antigens on microglia in chronic neurodegenerative diseases.
- To identify the presence and origin of ligands for these microglial receptors within the brain.
- To explore the potential role of immune-mediated processes and autodestruction in the pathogenesis of Alzheimer's disease and amyotrophic lateral sclerosis.
Main Methods:
- Analysis of microglial surface antigen expression.
- Identification of receptor ligands in brain tissue.
- Detection of complement system components, including the membrane attack complex (MAC).
- Association studies of complement regulatory proteins with neuronal damage.
Main Results:
- Microglia in AD and ALS exhibit upregulated expression of various leukocyte surface antigens and their corresponding ligands.
- Immunoglobulins and complement proteins are synthesized locally in the brain or enter from the bloodstream.
- The membrane attack complex (C5b-9) is found in AD and multiple sclerosis brain tissue, alongside protective proteins associated with neuronal damage in AD.
Conclusions:
- The expression of leukocyte antigens and ligands suggests an active immune response involving microglia and T lymphocytes in chronic neurodegenerative diseases.
- The presence of the membrane attack complex and associated regulatory proteins indicates complement-mediated damage to neurons.
- Autodestructive mechanisms may significantly contribute to the pathology observed in Alzheimer's disease and amyotrophic lateral sclerosis.