MURINE SCRAPIE-INFECTED NEURONS IN-VIVO RELEASE EXCESS PRION PROTEIN INTO THE EXTRACELLULAR-SPACE

An originally heretical proposition that the transmissible spongiform encephalopathies are caused by a host-coded protein (the prion hypothe sis) [18] is now current dogma. Indeed these disorders are commonly ca lled prion diseases [9,24] but the prion hypothesis provides no readil y acceptable explanation for the source of the informational component of the agent necessary to code for the diversity of strains of scrapi e [2,3,10]. Ultrastructural immunolocalisation of prion protein (PrP) in murine scrapie shows that PrP accumulates in association with the p lasmalemma of neurones, diffusing from the neuronal cell surface into the extracellular space around small neurites prior to aggregation and fibril assembly. These events occur without the involvement of other cell types. The area of neuropil infiltrated with extracellular PrP ar ound infected neurons and neurites indicates that the form of PrP init ially produced is not immediately amyloidogenic.