Neuropsychological function in patients with Gerstmann-Sträussler-Scheinker disease from the Indiana Kindred (F198S)

Abstract

Three patients with Gerstmann-Sträussler-Scheinker disease (GSS) caused by a serine-for-phenylalanine substitution at codon 198 of the prion protein gene (PRNP) were compared to 9 age- and education-matched non-mutation-carriers from the same large Indiana kindred (GSS–IK) on a comprehensive neuropsychological test battery. Clinically significant impairments in intelligence, secondary memory, attention and cognitive processing speed, executive ability, and manual motor skills were noted in 2 patients. The wide range and the severity of the cognitive deficits indicated generalized cerebral dysfunction consistent with global dementia. One patient, symptomatic for less than 1 year, had more selective deficits involving memory, motor skills, and verbal fluency, suggesting early subcortical involvement. (JINS, 1997, 3, 169–178.)

A New PRNP Mutation (G131V) Associated With Gerstmann-Sträussler-Scheinker Disease

“…The mutation reported herein is the first one to cause an amino acid substitution (G → V) in a short, antiparallel ␤-sheet domain comprising residues 128 to 131. 8 The impact of such mutation on PrP folding and processing remains undetermined. 14 In the proband, NFTs were observed in the hippocampus and entorhinal cortex.…”

Stability and Cu(II) Binding of Prion Protein Variants Related to Inherited Human Prion Diseases

“…More than 20 different mutations in the prion protein are known to be associated with inherited TSEs in humans (Collinge, 2001), i.e., the inherited form of CJD (Bell and Ironside, 1993;Spudich et al, 1995), the Gerstmann-Sträussler-Scheinker syndrome (GSS; Ghetti et al, 1995;Unverzagt et al, 1997), and fatal familial insomnia (FFI; Goldfarb et al, 1992;Gambetti et al, 1995). Interestingly, all disease-related point mutations in human PrP are located within segment 90-231, which forms the protease-resistant core of the PrP Sc oligomer (Safar et al, 1990, Weissmann et al, 1996.…”

Detection of tau in Gerstmann-Sträussler-Scheinker disease (PRNP F198S) by [18F]Flortaucipir PET

“…The PET tracer [ 18 F]flortaucipir was used to investigate the pattern of tau deposition in two GSS patients who carry the PRNP F198S mutation and are members of a pedigree that has been previously studied extensively from the clinical and neuropathological points of view [ 7 , 11 , 14 , 35 ].…”

“…Gerstmann-Sträussler-Scheinker disease (GSS) [ 9 ] is a rare dominantly inherited prion protein (PrP) amyloidosis. GSS patients, from a large kindred, have been extensively studied in three generations [ 13 ]; they carry a TTC to TCC DNA change at codon 198 of the prion protein gene ( PRNP) resulting in a phenylalanine to serine substitution (F198S) in the prion protein [ 6 , 7 , 11 , 12 , 14 , 16 , 35 ]. Neuropathologic examinations in these patients have shown that the extracellular PrP amyloid coexists with a severe intraneuronal tau pathology, characterized by deposits of hyperphosphorylated tau and neurofibrillary tangles (NFT) in the cerebral gray matter, but not in the cerebellum [ 10 , 11 , 14 ].…”

“…These neurologic symptoms may be preceded by psychiatric manifestations including drug dependence, depression, and/or psychosis [ 7 ]. As the disease progresses, memory impairment and cognitive dysfunction become severe [ 35 ].…”