Amyloid plaques in Creutzfeldt‐Jakob disease stain with prion protein antibodies

Abstract

Amyloid plaques are found in the brains of some patients with Creutzfeldt-Jakob disease (CJD) and all patients with a related transmissible disorder, Gerstmann-Sträussler syndrome (GSS). In scrapie, a prion disease of animals, amyloid plaques have been shown to be composed of prion proteins (PrP), which form filaments of relatively uniform diameter. We report here that antisera raised against hamster scrapie PrP specifically stain amyloid plaques in the brains of both humans and rodents with CJD as well as a human subject with GSS. Earlier studies showed that these antibodies react with both rodent and human CJD PrP. The immunostained congophilic amyloid plaques in rodent brains measured 10 to 30 micron in diameter and exhibited a Maltese cross appearance. Limited proteolysis enhanced immunostaining of amyloid plaques in human brain sections from patients with CJD or GSS. Presumably proteolysis increases the exposure of those epitopes shared by human and rodent PrP. The differences in immunoreactivity between rodent and human amyloid plaques are consistent with other findings showing that cellular genes, not infectious purified prions, encode PrP.

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

“…PrPsc has been generally distinguished from cellular PrP (PrPC) by its relative protease resistance, its insolubility in nondenaturing detergents, its enhanced antigenicity after denaturation, and its posttranslational biogenesis; spectroscopic studies show that the two proteins differ in their conformations (23). When amyloid plaques are present in these patients, the plaques stain with anti-PrP antibodies (24)(25)(26).…”

Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.

“…PrP 27-30 was subsequently shown to be derived by limited proteolysis from a larger protein designated PrPSc, which is encoded by a chromosomal gene and not by a putative nucleic acid within the prion (2,44). Although many biochemical (6,44,51), genetic (2,7,65), and pathological (4,5,36,52) results argue persuasively that PrPsc is a component of the infectious scrapie particle, only recently have immunoaffinity chromatography and neutralization data been obtained that establish that this is indeed the case (22a). Dispersion of prions into detergent-lipid-protein complexes permitted purification of scrapie infectivity by a PrP monoclonal antibody affinity column as well as neutralization with polyclonal PrP 27-30 antibodies.…”

“…One of the major problems facing investigators studying most neurodegenerative diseases is the lack of animal models that recapitulate all features of these disorders (23). Although Alzheimer's disease is not transmissible (25) and its amyloid does not contain detectable amounts of PrP (36,52), biochemical processes similar to those in prion diseases may be involved. Posttranslational modification of a normal cellular protein to an abnormal polymerizing isoform may be a process common to several degenerative diseases, and initiation of the pathological cascade could be caused by defects in the protein gene itself or in "incubation time" loci, as well as by environmental insults.…”

Prions, amyloids, and RNA: Pieces of a puzzle

“…15,27 Furthermore, histopathological studies of brains of scrapie-infected animals and Creutzfeldt-Jakob disease patients revealed the accumulation of PrP Sc in congophilic amyloid plaques. 28,29 Finally, in vitro, PrP formed rod-like aggregates that exhibited apple-green birefringence upon binding Congo Red. 30 With these characteristics being major hallmarks of amyloids, experimental evidence indicated that PrP was an amyloidogenic protein.…”