Morphometric analysis of microglia in Alzheimer's disease
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A F Carpenter1, P W Carpenter, W R Markesbery
1Department of Pathology, University of Kentucky Medical Center, Lexington.
Abstract:
HLA-DR-immunoreactive microglia were quantitated in the middle temporal gyrus of five late-stage patients with Alzheimer's disease (AD) and five age-matched control subjects using LN3 immunocytochemistry and computerized morphometric image analysis. The grand mean numerical density of HLA-DR-immunoreactive microglia in AD (403.86/mm2) was significantly larger than in the five control subjects (193.33/mm2) (p < 0.0001). The grand mean cross-sectional area of HLA-DR-immunoreactive microglia in AD subjects (222.90 microns2) was significantly larger than in control subjects (121.59 microns2) (p < 0.0001). The percentage of total microglia that were large activated microglia was much greater in AD (47.9%) than in control subjects (15.2%). The grand mean percent of the cortical area occupied by HLA-DR-immunoreactive microglia in AD (9.02%) was significantly greater than in controls (2.35%) (p < 0.0001). Microglia were present in greater numbers in the outer three cortical laminae in both AD and controls. The striking increase in activated microglia in the neocortex and their role in the inflammatory response and possible secretion of neurotoxins could be important in neuron degeneration in AD.
Insights
Alzheimer's disease (AD) shows significantly increased numbers and activation of microglia, immune cells in the brain. This heightened microglial response may contribute to neurodegeneration in AD patients.
Area of Science:
- Neuroscience
- Immunology
- Neuropathology
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline.
- Microglia, the resident immune cells of the central nervous system, play a role in neuroinflammation.
- The activation state and density of microglia in AD are not fully understood.
Purpose of the Study:
- To quantify and characterize HLA-DR-immunoreactive microglia in the middle temporal gyrus of AD patients and controls.
- To investigate the relationship between microglial activation and Alzheimer's disease pathology.
Main Methods:
- Utilized LN3 immunocytochemistry to identify HLA-DR-immunoreactive microglia.
- Employed computerized morphometric image analysis for quantitative assessment.
- Compared AD patients (n=5) with age-matched control subjects (n=5).
Main Results:
- Significantly higher numerical density of HLA-DR-immunoreactive microglia in AD brains (403.86/mm2) compared to controls (193.33/mm2).
- Larger cross-sectional area of microglia in AD (222.90 microns2) versus controls (121.59 microns2), indicating activation.
- A greater percentage of large, activated microglia in AD (47.9%) than in controls (15.2%).
- Increased cortical area occupied by microglia in AD (9.02%) compared to controls (2.35%).
Conclusions:
- Alzheimer's disease is associated with a substantial increase in activated microglia in the neocortex.
- Activated microglia may contribute to neurodegeneration through inflammatory responses and neurotoxin secretion.
- These findings highlight the role of neuroinflammation in AD pathogenesis.