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MHC class II-positive microglia in human brain: association with Alzheimer lesions
L S Perlmutter1, S A Scott, E Barrón
1Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033.
Abstract:
Cells of the mononuclear phagocytic system (MPS) present foreign antigen on their cell surfaces bound to major histocompatibility complex (MHC) class II molecules. Previous studies of normal human brain samples reported MHC class II expression primarily by perivascular MPS cells and white matter microglial cells. Marked increases in MHC class II-expressing microglia have been shown in many neuropathologic disorders, including Alzheimer's disease (AD). A close morphologic association between these cells and Alzheimer senile plaque beta-amyloid has been demonstrated. The present study used a mixed aldehyde fixative to enhance the localization of MHC class II-expressing MPS cells in non-AD and AD brain. Two antibodies against MHC class II (HLA-DR; LN3), as well as the lectin Ricinus communis agglutinin (which recognizes both ramified and activated microglia) were used for light and electron microscopic analyses. We now report that MHC class II-expressing ramified microglia are distributed in a uniform reticular array throughout the grey, as well as the white matter in non-AD cases. In AD cases, immunolabelled cells had the morphology of activated microglia, with darkly stained plump somata and short, thick processes. Microglia clustered around senile plaque amyloid and neurofibrillary tangles (NFT), rather than forming the uniform array characteristic of control tissue. Finally, we report that perivascular MPS cells are found in a morphologic relationship with vascular amyloid identical to that seen between microglial cells and senile plaque beta-amyloid. These data suggest that MHC class II-expressing cells may be involved in the degradation of NFT-laden neurons and the posttranslational modification of extracellular-NFT epitopes. In addition, both parenchymal and perivascular MPS cells are ideally situated to uptake and process the beta-amyloid protein precursor and deposit beta-amyloid on senile plaques, NFT, and the cerebrovasculature.
Insights
In Alzheimer's disease (AD), brain immune cells expressing major histocompatibility complex (MHC) class II molecules change from a uniform distribution to clustering around amyloid plaques and neurofibrillary tangles. These cells may play a role in processing amyloid and other AD-related proteins.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Mononuclear phagocytic system (MPS) cells, including microglia, express major histocompatibility complex (MHC) class II molecules.
- MHC class II expression is increased in microglia in neuropathologic disorders like Alzheimer's disease (AD).
- Microglia show a close association with senile plaque beta-amyloid in AD brains.
Purpose of the Study:
- To investigate the distribution and morphology of MHC class II-expressing MPS cells in non-AD and AD human brains.
- To characterize the relationship between these immune cells and AD neuropathology, including amyloid plaques and neurofibrillary tangles (NFT).
Main Methods:
- Used a mixed aldehyde fixative for enhanced localization of MHC class II-expressing cells.
- Employed antibodies against MHC class II (HLA-DR; LN3) and Ricinus communis agglutinin lectin.
- Conducted light and electron microscopic analyses on non-AD and AD brain tissues.
Main Results:
- In non-AD brains, MHC class II-expressing ramified microglia formed a uniform array in grey and white matter.
- In AD brains, microglia exhibited activated morphology and clustered around senile plaque amyloid and neurofibrillary tangles (NFT).
- Perivascular MPS cells showed a similar association with vascular amyloid as microglia with parenchymal amyloid.
Conclusions:
- MHC class II-expressing cells, including microglia and perivascular MPS cells, are altered in AD.
- These cells may be involved in the degradation of NFT-laden neurons and extracellular NFT epitopes.
- MPS cells are strategically positioned to process beta-amyloid precursor and contribute to amyloid deposition in AD.