Molecular, Cellular, and Pathologic Characterization of HLA-DR Immunoreactivity in Normal Elderly and Alzheimer's Disease Brain

Previous studies have suggested that markers of immune function may be present in brain. We have characterized one of the most important of these markers, the human major histocompatibility complex antigen HLA-DR, at molecular, cellular, and pathologic levels. The results show that an antigen with the correct molecular weight for HLA-DR and the appropriate immunoreactivity for HLA-DR monoclonal antibodies is present in nondemented elderly (ND) and Alzheimer's disease (AD) brain tissue. HLA-DR immunoreactivity is profusely expressed by brain microglia, often expressed by lymphocytes within the neuropil, rarely expressed by astrocytes, and not expressed by neurons or oligodendrocytes. Pathologically, HLA-DR-like staining in ND patients is confined primarily to white matter nonreactive or resting microglia. In AD patients, both white matter and gray matter are stained, and HLA-DR-positive reactive microglia predominate. Virtually all senile or neuritic plaques are densely HLA-DR immunoreactive: at the plaque core staining intensity is elevated as much as 50-fold, dropping to background at the plaque margin.