MICROGLIA AND THE DEVELOPMENT OF SPONGIFORM CHANGE IN CREUTZFELDT-JAKOB-DISEASE

Recent in vitro experiments suggest that neurotoxicity of the prion pr otein is dependent on the presence of microglia. We have studied 11 ca ses of Creutzfeldt-Jakob disease (CJD) using immunocytochemistry in co mbination with computerized image analysis to clarify the relationship between spongiform change and microglial activation. MHC class II-pos itive microglia were almost exclusively confined to cortical gray matt er where the neuropil area occupied by these cells exceeded that of co ntrols more than 350-fold. In cortical regions with a bimodal distribu tion of spongiform degeneration, the presence of class II-positive mic roglia correlated well with the presence of vacuolation in layer V, bu t significantly less with spongiform change in layers II and III. In a reas where spongiform degeneration affected the entire depth of the co rtex, activated microglia were predominantly located in the inner one- half of the cortex or were evenly distributed throughout all cortical laminae. Here, microglia exhibited atypical, tortuous cell processes a nd occasionally intracytoplasmic vacuoles, suggesting that microglia t hemselves may become a disease target. Taken together, our results pro vide indirect evidence against an early causative involvement of micro glia in the development of spongiform change. At later stages, however , diseased microglia could produce harmful factors which mediate both astrogliosis and neuronal injury.