Early destruction of the extracellular matrix around parvalbumin-immunoreactive interneurons in Creutzfeldt-Jakob disease

GABA-interneurons immunoreactive (IR) for the calcium-binding protein parva lbumin are lost during the early stages of Creutzfeldt-Jakob disease (CJD) and diminution in their number may partially account for the neurological d isturbances manifested in patients suffering from this condition. The disea se is characterized by a transformation of the prion protein, PrPc-a host-c oded sialoglycoprotein-to its protease-resistant and putatively pathologica l form, PrPCJD. And since this conversion is likely to take place at the ce ll surface, we were curious to know whether the "perineuronal net"-a charac teristic accumulation of extracellular matrix in intimate contact with the surface of parvalbumin-IR neurons-is implicated in the early disappearance of the mantled cells. Using various lectins and antibodies as markers for t he perineuronal net in brains of 21 CJD victims, we observed that this mesh work of extracellular matrix molecules is lost before the embraced parvalbu min-IR neurons themselves disappear. Hence, an interaction of PrPc and/or P rPCJD with components of the extracellular matrix around this subpopulation of nerve cells precipitates a sequence of as yet unknown events which culm inates in the replacement of perineuronal nets by deposits of insoluble PrP CJD. This change in the environment of the GABA-interneurons in for parvalb umin may ultimately provoke their death. (C) 1999 Academic Press.