Gerstmann-Straüssler-Scheinker PRNP P102L-129V mutation

Abstract

Neuropathological and biochemical studies in a case of Gerstmann-Straüssler-Scheinker disease bearing the PRNP P102L-129V mutation showed numerous multicentric PrP res in the cerebral cortex, striatum, thalamus and cerebellum, PrP res globular deposits in the anterior and posterior horns of the spinal cord, and multiple granular PrP res deposits in the grey and white matter of the encephalon and spinal cord. Western blots with antiPrP res antibodies revealed several weak bands ranging from 36 to 66 kDa, weak bands of 29 and 24 kDa, a strong band of about 20 kDa, a low band of molecular weight around 15 kDa and a weaker band of about 7 kDa. Spongiform degeneration was absent. Hyper-phosphorylated 3R and 4R tau occurred in dystrophic neurites surrounding PrP res plaques, neuropil threads and, to a lesser degree, in the form of neurofibrillary tangles. Gel electrophoresis of sarkosyl-insoluble fractions and western blotting with anti-phospho-tau antibodies showed a pattern similar to that seen in Alzheimer disease cases run in parallel. Dystrophic neurites in the vicinity of PrP res plaques were enriched in voltage dependent anion channel thus suggesting abnormal accumulation of mitochondria. These changes were associated with increased oxidative damage in neurons and astrocytes, Finally, increased expression of active stress kinases, that have the capacity to phosphorylate tau in vitro, p38 (p-38-P) and SAPK/ JNK (SAPK/JNK-P) was found in cell processes surrounding PrP plaques. Together, these observations provide evidences of mitochondrial abnormalities, and increased oxidative stress damage and oxidative stress responses in GSS bearing the PRNP P102L-129V mutation.

Cellular Prion Protein Combined with Galectin-3 and -6 Affects the Infectivity Titer of an Endogenous Retrovirus Assayed in Hippocampal Neuronal Cells

“…The larger plaques seen in P101L would be related to greater enhancement of replication by the mutant sequence. In GSS cases, P102L PRNP mutation with M129V and A117V PRNP mutation are reported to enhance plaque numbers in the brain [42, 43]. Plaques and PrP correlation is so far only prion diseases issue and no reports related with other viral diseases so far.…”

Extracellular Amyloid Deposits in Alzheimer’s and Creutzfeldt–Jakob Disease: Similar Behavior of Different Proteins?

“…These larger cores tend to be surrounded by smaller amyloid deposits [156]. Like the previously mentioned plaques, they can be observed with hematoxylin-eosin staining [164]. GSS in comorbidity with primary age-related tauopathy (PART).…”

Description of the first Spanish case of Gerstmann–Sträussler–Scheinker disease with A117V variant: clinical, histopathological and biochemical characterization

“…Neuropathological findings are also quite diverse although the most characteristic feature is the presence of multicentric amyloid plaques derived from abnormal PrP products that are mainly distributed in the cerebral cortex, basal ganglia, and cerebellum. Unusual characteristics include the presence of neurofibrillary tangles formed of hyperphosphorylated tau, which have been reported in some GSS cases linked to specific pathogenic variants [ 5 – 8 ]. The exact incidence of the disease is unknown since familial clusters are not systematically reported.…”