• Adult
• Female
• Humans
• Male
• Middle Aged
• Young Adult
• Adaptor Proteins, Signal Transducing/genetics
• Cerebellar Ataxia/diagnostic imaging
• Cerebellar Ataxia/genetics
• Cohort Studies
• DNA Mutational Analysis
• Haplotypes
• Magnetic Resonance Imaging
• Pedigree
• Taiwan

• 112-2314-B-075-034-MY3 National Science and Technology Council, Taiwan
• 113-2634-F-039-001 National Science and Technology Council, Taiwan
• Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B)
• Brain Research Center
• National Science and Technology Council, Taiwan

• Asia
• Creutzfeldt Jakob disease
• genetic CJD
• genetic prion diseases
• latrogenic CJD
• sporadic CJD

• Humans
• Creutzfeldt-Jakob Syndrome/genetics
• Prions/genetics
• Prion Proteins
• Asia

• Gerstmann-Sträussler-Scheinker syndrome
• P102L
• PRNP gene
• prion disease
• spinocerebellar ataxia (SCA)

• University Natural Science Research Project of Anhui Province
• Anhui University of Chinese Medicine

• Creutzfeldt–Jakob disease (CJD)
• Gerstmann–Sträussler–Scheinker disease (GSS)
• fatal familial insomnia (FFI)
• mutation
• prion
• risk modifiers

• Humans
• Prions/genetics
• Prion Diseases/genetics
• Prion Diseases/diagnosis
• Japan/epidemiology
• Prion Proteins/genetics
• Gerstmann-Straussler-Scheinker Disease/genetics
• Creutzfeldt-Jakob Syndrome/genetics
• Mutation

Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called “prion”, which corresponds to a pathological form (PrP^Sc) of a normal cellular protein (PrP^C) expressed in nerve cells. PrP^Sc is resistant to degradation and can induce abnormal folding of PrP^C, and TSEs are characterized by extensive spongiosis and gliosis and the presence of PrP^Sc amyloid plaques. CJD presents initially with clinical symptoms similar to Alzheimer’s disease (AD). In AD, tau aggregates and amyloid-β protein plaques are associated with memory loss and cognitive impairment in patients.

In this work, we study the role of tau and its relationship with PrP^Sc plaques in CJD.

Multiple immunostainings with specific antibodies were carried out and analyzed by confocal microscopy.

We found increased expression of the glial fibrillary acidic protein (GFAP) and matrix metalloproteinase (MMP-9), and an exacerbated apoptosis in the granular layer in cases with prion disease. In these cases, tau protein phosphorylated at Thr-231 was overexpressed in the axons and dendrites of Purkinje cells and the extensions of parallel fibers in the cerebellum.

We conclude that phosphorylation of tau may be a response to a toxic and inflammatory environment generated by the pathological form of prion.

• tau protein
• Cerebellum
• neuronal death
• prion encephalopathy
• prion protein

• disease duration
• human prion diseases
• incidence
• mortality
• spongiform encephalopathy

Background: A novel prion variant, PRNP p.Tyr225Cys (c.674A>G; p.Y225C), was identified in an atypical Creutzfeldt–Jakob disease (CJD) patient. The patient had a 5-year history of progressive cognitive impairment with speech and gait disturbances. From the basic neurological examination at his first hospital visit, rigidity and myoclonic jerks in all limbs were observed without focal weakness. Electroencephalogram showed the diffuse slow continuous delta activity in the bilateral cerebral hemisphere. Magnetic resonance imaging revealed abnormalities in the brain, such as cortical signal changes and edema in the frontotemporoparietal lobes and the basal ganglia. Cerebrospinal fluid 14–3-3 protein analysis showed a weakly positive signal. Family history remained unclear, but the patient’s mother and sister were diagnosed with cognitive impairment but both refused genetic testing.

Methods: Targeted next generation sequencing (NGS) was performed on 50 genes, involved in different neurodegeneratives diseases, such as Alzheimer's, Parkinson's, frontotemporal dementia or prion diseases. In silico analyses and structure predictions were performed on the potential patohgenic mutations.

Results: NGS and standard sequencing revealed the novel PRNP p.Tyr225Cys mutation in the patient. Structure predictions revealed that this may make the helix more flexible. In addition, the extra cysteine residue in TM-III of prion protein may result in disturbances of natural disulfide bond.

Conclusion: Hence, the pathogenicity of PRNP p.Tyr225Cys was not fully confirmed at present, and its penetrance was suggested to be low. However, its possible pathogenic nature in prion diseases cannot be ignored, since Tyr/Cys exchange could disturb the helix dynamics and contribute to conformational alteration and disease progression.

• Gerstmann–Sträussler–Scheinker syndrome
• PRNP
• Tyr225Cys mutation
• atypical Creutzfeldt–Jakob disease
• diagnosis
• prion
• sequencing

Gerstmann-Sträussler-Scheinker syndrome (GSS) is an exceedingly rare prion disease. There are only 3 case reports of GSS in China. Here we report the first GSS family in southern China. A 47-year-old female complained of unsteady gait and dysarthria. Seven other individuals presented similar symptoms in 3 generations of her family, and all died 4–6 years after onset. To detect causative mutations, we employed a gene analysis panel of hereditary diseases. This revealed a P102L mutation in the prion protein gene (PRNP) gene, which is commonly found in GSS featuring cerebellar ataxia. However, GSS is an uncommon cause of hereditary cerebellar ataxia that might be overlooked because many neurologists are unfamiliar with it. To avoid misdiagnosis in the patients with hereditary cerebellar ataxia, GSS should be taken into account if other causes are absent, especially in patients that have accompanying psychiatric symptoms and a short survival time.

Gerstmann-Sträussler-Scheinker (GSS) disease is an inherited prion disease that is clinically characterized by the early onset of progressive cerebellar ataxia. The incidence of GSS is extremely low and it is particularly rare in China. Therefore, clinicians may easily confuse this disease with other diseases that also cause ataxia, resulting in its under-diagnosis or misdiagnosis.

Here, we report the first case of genetically diagnosed GSS disease in Northeast China. The patient exhibited typical ataxia and dysarthria 2.5 years after symptom onset. However, magnetic resonance imaging of the brain and spinal cord revealed a normal anatomy. Screening results for the spinocerebellar ataxia gene were also negative. We thus proposed to expand the scope of genetic screening to include over 200 mutations that can cause ataxia. A final diagnosis of GSS was presented and the patient was followed for more than 3.5 years, during which we noted imaging abnormalities. The patient gradually exhibited decorticate posturing and convulsions. We recommended administration of oral sodium valproate, which resolved the convulsions.

Patients with inherited ataxia should be considered for a diagnosis of GSS via genetic testing at an early disease stage.

• Prion disease
• Cerebellar ataxia
• Magnetic resonance imaging
• Diagnosis
• Brain
• Case report

• PRNP
• amyloid
• neuritic plaques
• neurofibrillary tangles
• prion disease
• prion protein
• spongiform encephalopathy
• tau protein
• transmissibility

• Alzheimer’s disease
• Creutzfeldt–Jakob disease
• Gerstmann–Sträussler–Scheinker disease
• PRNP gene
• diagnosis
• fatal familial insomnia
• genetics
• mutation
• prion

• Easy Z-score analysis
• MRI
• P102L
• SEPCT
• VSRAD