Antibodies to a scrapie prion protein

Abstract

Scrapie is a slow infection of the nervous system which progresses in the absence of any apparent immune response. The recent development of a large-scale purification protocol for scrapie prions made it possible to obtain substantial quantities of electrophoretically purified prion protein (PrP 27-30) and we report here on the successful production of a rabbit antiserum to PrP 27-30. The antiserum reacted with PrP 27-30 and several lower molecular weight proteins as shown by Western blots; it did not react with protein preparations from uninfected brains. Discrete structures in the subependymal region of scrapie-infected hamster brains were stained immunocytochemically. These same structures also stained with Congo red dye and showed green birefringence with polarized light, a characteristic of purified prion rods. This staining pattern suggests that they are amyloid plaques.

Copurification of Sp33-37 and Scrapie Agent from Hamster Brain Prior to Detectable Histopathology and Clinical Disease

“…5 e). They were localized to periventricular and subependymal sites, in agreement with previous observations (Bendheim et al, 1984;DeArmond et al, 1987). At 77 days the number of plaques had increased considerably in those sites and additionally some were detected in the anterior thalamus.…”

“…Amyloid plaques were discovered to be a component of the pathology of experimental scrapie in hamsters when antibodies to Sp33-37 were used in immunohistochemical staining of scrapie-affected brain (Bendheim et al, 1984). These antibodies have consistently localized the amyloid plaques in extracellular spaces in periventricular, subependymal, subpial and perivascular sites (Bendheim et al, 1984;DeArmond et al, 1987).…”

“…thioflavin, Congo red, or antibodies to the scrapie agent protein (1 : 500 dilution) (Bendheim et al 1984) to determine the extent of accumulation of this protein in amyloid plaques. The coded sections were examined and scored for pathology, then the code was broken and the sections were re-examined.…”

“…Sp33-37 aggregates into readily sedimentable forms during isolation. In vivo, at least some Sp33-37 is present in amyloid fibrils that coalesce to form amyloid plaques (Bendheim et al, 1984;DeArmond et al, 1985). The amyloid fibrils have been designated scrapie-associated fibrils (SAF) or prion rods by different groups (Merz et al, 1981(Merz et al, , 1983(Merz et al, , 1984Barry et al, 1985;McKinley et al, 1986).…”

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

“…41,42 Such fibrils, which are self-propagating protein conformations occurring both in vitro and in vivo, [43][44][45][46][47][48][49][50] are thus transmissible. When small nuclei or fibril seeds are present, they dramatically accelerate fibril formation by inducing conformational changes in amyloid protein monomers.…”