A special report I. Prion protein (Prp)--amyloid plaques in the transmissible spongiform encephalopathies (TSEs) or prion disease revisited.

We present a retrospective analysis of PrP-amyloid plaques encountered in CJD and GSS. In human TSEs (kuru, CJD and GSS) several PrP-immunopositive plaques and plaque-like deposits were detected. In kuru, plaques were typical "kuru" plaques--stellate structures deposited mostly in the granular and Purkinje cell layer of the cerebellum. Many smaller or larger clusters were visible but, in contrast to GSS, they never have merged together to form multicentric plaques. In all cases of GSS, plaques were located in the granular and Purkinje cell layer and in the molecular layer. There were many different forms of plaques: from kuru plaques (unicentric stellate plaques) to clusters of unicentric plaques which by merging eventually formed "multicentric plaques". The latter are the hallmark of this disease. By electron microscopy several types of amyloid plaques, which corresponded to those seen by PrP immunohistochemistry were observed. The first type, unicentric kuru plaque consisted of stellate arrangements (stars or cores) of amyloid bundles emanating from a densely interwoven center. Amyloid stars were surrounded by astrocytic processes and invaded by microglial cells but dystrophic neurites were only rarely seen. In contrast multicentric plaques were often surrounded by dystrophic neurites. The rarest type of plaque, were neuritic plaques. In 263K and 22C-H scrapie-infected hamster brains, on the light microscopy of the semi-thin (1 micron) sections, discrete PrP-immunopositive plaques were observed in the subependymal region but not in the deep brain neuroparenchyma. These plaques were not discernible by routine HE staining. Ultrastructurally, plaques were recognized as areas of low electron density containing haphazardly-oriented fibrils and not as stellate compact structures typical of plaques in human cases of CJD and GSS. These plaques were located beneath the basal border of the ependymal cells and adjacent blood vessels. Occasional dystrophic neurites containing electron-dense inclusion bodies were seen within the plaque perimeter, which always remained PrP-negative.