MICROGLIA IN DIFFUSE PLAQUES IN HEREDITARY CEREBRAL-HEMORRHAGE WITH AMYLOIDOSIS (DUTCH) - AN IMMUNOHISTOCHEMICAL STUDY

In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) b eta/A4 amyloid deposition is found in meningocortical blood vessels an d in diffuse plaques in the cerebral cortex. Diffuse plaques putativel y represent early stages in the formation of senile plaques. Microglia are intimately associated with congophilic plaques in Alzheimer's dis ease (AD), but microglial involvement in diffuse plaque formation is c ontroversial. Therefore, we studied the relationship between microglia and diffuse plaques in the cerebral cortex of four patients with HCHW A-D using a panel of macrophage/microglia markers (mAbs LCA, LeuM5, Le uM3, LN3, KP1, OKla, CLB54, Mac1, Ki-M6, AMC30 and the lectin RCA-1). Eight AD patients, one demented Down's syndrome (DS) patient and four non-demented controls were included for comparison. In controls and HC HWA-D patients ramified or ''resting'' microglia formed a reticular ar ray in cortical gray and subcortical white matter. Microglial cells in or near HCHWA-D diffuse plaques retained their normal regular spacing and ramified morphology. In AD/DS gray matter more microglial cells w ere stained than in controls and HCHWA-D patients. Intensely immunorea ctive microglia with enlarged cell bodies and short, thick processes c lustered in congophilic plaques. In contrast to the resting microglia, these ''activated microglia'' strongly expressed class II major histo compatibility complex antigen, HLA-DR, and were AMC30-immunoreactive. These findings support the view that microglia play a role in the form ation of congophilic plaques but do not initiate diffuse plaque format ion. Another finding in this study is the presence of strong monocyte/ macrophage marker immunoreactivity in the wall of cortical congophilic blood vessels in HCHWA-D.