Anti-PRNP (aa 142-153) polyclonal antibody

Objective To describe the clinicopathologic, molecular, and transmissible characteristics of genetic prion disease in a young man carrying the PRNP-G114V variant. Methods We performed genetic, histologic, and molecular studies, combined with in vivo transmission studies and in vitro replication studies, to characterize this genetic prion disease. Results A 24-year-old American man of Polish descent developed progressive dementia, aphasia, and ataxia, leading to his death 5 years later. Histologic features included widespread spongiform degeneration, gliosis, and infrequent PrP plaque-like deposits within the cerebellum and putamen, best classifying this as a Creutzfeldt-Jakob disease (CJD) subtype. Molecular typing of proteinase K-resistant PrP (resPrP(Sc)) revealed a mixture of type 1 (similar to 21 kDa) and type 2 (similar to 19 kDa) conformations with only 2, rather than the usual 3, PrPSc glycoforms. Brain homogenates from the proband failed to transmit prion disease to transgenic Tg(HuPrP) mice that overexpress human PrP and are typically susceptible to sporadic and genetic forms of CJD. When subjected to protein misfolding cyclic amplification, the PrPSc type 2 (similar to 19 kDa) was selectively amplified. Conclusions The features of genetic CJD(G114V) suggest that residue 114 within the highly conserved palindromic region (113-AGAAAAGA-120) plays an important role in prion conformation and propagation.

A Corriedale ewe was confirmed as the first atypical scrapie case during an active surveillance program for transmissible spongiform encephalopathies in small ruminants in Japan. The animal was homozygous for the AF(141)RQ haplotype of PRNP. The animal showed clinical neurological signs possibly due to listeriosis before culling. Western blot analysis showed an unusual multiple banded pattern with a low-molecular fragment at similar to 7 kDa. Histopathology revealed suppurative meningoencephalitis caused by listeriosis in the brainstem. Fine granular to globular immunostaining of disease-associated prion proteins was mainly detected in the neuropil of the spinal tract of the trigeminal nerve and in the white matter of the spinocerebellar tract. Based on these results, this case was conclusively diagnosed as atypical scrapie with encephalitic listeriosis.