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Microglial interleukin-1 alpha expression in brain regions in Alzheimer's disease: correlation with neuritic plaque
J G Sheng1, R E Mrak, W S Griffin
1Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, USA.
Abstract:
Interleukin-1 alpha-immunoreactive (IL-1 alpha+) microglia are prominent components of neuritic plaques in Alzheimer's disease, and may be important in the evolution of neuritic plaques from diffuse amyloid deposits. Neuritic plaques show a characteristic distribution across cerebral regions and are absent in the cerebellum of patients with Alzheimer's disease. We used single- and dual-immunohistochemical labelling to investigate the possibility that the expression of IL-1 alpha is correlated with this regional distribution of neuritic (tau 2-immunoreactive, tau 2+) plaques. In Alzheimer's disease, tau 2+ neuritic plaques occurred with increasing frequency in grey matter of frontal and occipital lobes, temporal lobe, and hippocampus. There were positive correlations between the regional patterns of distribution of activated IL-1 alpha+ microglia and tau 2+ neuritic plaques as well as between activated IL-1 alpha+ microglia and activated astrocytes. No activated IL-1 alpha+ microglia, tau 2+ neuritic plaques, or activated astrocytes were observed in cerebellum of these Alzheimer patients. These regional relationships between activated IL-1 alpha+ microglia, tau 2+ neuritic plaques, and activated astrocytes, together with the established functions of IL-1, support a causal association between the overexpression of IL-1 and the evolution of beta-amyloid deposits into neuritic plaques in Alzheimer's disease.
Insights
Interleukin-1 alpha (IL-1 alpha) expressing microglia correlate with neuritic plaque development in Alzheimer's disease brains. This suggests IL-1 alpha may drive the progression of amyloid deposits into these characteristic plaques.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Interleukin-1 alpha (IL-1 alpha)-immunoreactive microglia are key components of Alzheimer's disease (AD) neuritic plaques.
- These microglia may play a role in the transformation of diffuse amyloid deposits into neuritic plaques.
- Neuritic plaques exhibit a distinct regional distribution in AD brains, notably absent in the cerebellum.
Purpose of the Study:
- To investigate the correlation between Interleukin-1 alpha (IL-1 alpha) expression and the regional distribution of neuritic (tau 2-immunoreactive, tau 2+) plaques in Alzheimer's disease.
- To explore the relationship between activated IL-1 alpha+ microglia, neuritic plaques, and activated astrocytes.
Main Methods:
- Employed single- and dual-immunohistochemical labeling techniques.
- Analyzed the regional distribution of tau 2+ neuritic plaques and IL-1 alpha+ microglia in Alzheimer's disease brains.
- Assessed the presence of activated astrocytes in conjunction with microglia and plaques.
Main Results:
- Neuritic plaques (tau 2+) increased in frequency in the frontal, occipital, temporal lobes, and hippocampus.
- Positive correlations were observed between the regional distribution of activated IL-1 alpha+ microglia and tau 2+ neuritic plaques.
- Activated IL-1 alpha+ microglia also correlated with activated astrocytes; neither was found in the cerebellum.
Conclusions:
- The regional co-distribution supports a causal link between IL-1 alpha and the evolution of beta-amyloid deposits into neuritic plaques.
- Overexpression of IL-1 is implicated in the pathogenesis of neuritic plaque formation in Alzheimer's disease.
- Activated microglia and astrocytes, mediated by IL-1, are integral to Alzheimer's neuropathology.