An autopsy case of Creutzfeldt-Jakob disease with a V180I mutation of the PrP gene and Alzheimer-type pathology

Yoshida, Hidenori; Terada, Seishi; Ishizu, Hideki; Ikeda, Kenji; Hayabara, Toshiyuki; Ikeda, Kazuyo; Deguchi, Kazushi; Touge, Tetsuo; Kitamoto, Tetsuyuki; Kuroda, Shigetoshi

doi:10.1111/j.1440-1789.2009.01048.x

Cited by 32 publications

(46 citation statements)

References 24 publications

(76 reference statements)

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“…The period from disease onset to death was longer in V180I-MM than in sCJD-MM1, as previously reported,4 but was almost the same as in sCJD-MM2 (table 2). Among the 16 total autopsied patients with V180I in this cohort, few patients had additional neuropathological alterations such as Alzheimer's disease 6 7. There was no difference between definite and probable or possible cases with V180I mutation.…”

Section: Resultsmentioning

confidence: 77%

Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene

et al. 2014

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ObjectivesGenetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein gene (PRNP) is of great interest because of the differences from sporadic CJD and other genetic prion diseases in terms of clinical features, as well as pathological and biochemical findings. However, few systematic observations about the clinical features in patients with this unique mutation have been published. Therefore, the goal of this study was to relate this mutation to other forms of CJD from a clinical perspective.DesignWe analysed clinical symptoms, prion protein genetics, biomarkers in cerebrospinal fluid (CSF) and MRI of patients.Participants186 Japanese patients with the V180I mutation in PRNP.ResultsOur results indicate that the V180I mutation caused CJD at an older age, with a slower progression and a lower possibility of developing myoclonus, cerebellar, pyramidal signs and visual disturbance compared with classical sporadic CJD with methionine homozygosity at codon 129 of PRNP. Cognitive impairment was the major symptom. Diffuse hyperintensity of the cerebral cortex in diffusion-weighted MRI might be helpful for diagnosis. Owing to the low positivity of PrPSc in the CSF, genetic analysis was often required for a differential diagnosis from slowly progressive dementia.ConclusionsWe conclude that the V180I mutation in PRNP produces a late-developing and slow-developing, less severe form of CJD, whose lesions are uniquely distributed compared with sporadic and other genetic forms of CJD.

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Section: Resultsmentioning

confidence: 77%

Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene

et al. 2014

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“…Specifically, the co-existence of PrP Sc and Aβ in patients with clinical manifestation of both AD and TSE has been extensively reported (Haraguchi et al, 2009; Muramoto et al, 1992; Tsuchiya et al, 2004; Yoshida et al, 2009). PrP has been identified in senile plaques of AD patients and Aβ aggregates have been found within PrP deposits in patients affected with CJD or Gertsmann-Straussler-Scheinker syndrome (Bugiani et al, 1993; Hainfellner et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases

et al. 2010

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The central event in protein misfolding disorders (PMDs) is the accumulation of a misfolded form of a naturally expressed protein.Despite the diversity of clinical symptoms associated with different PMDs, many similarities in their mechanism suggest that distinct pathologies may cross talk at the molecular level. The main goal of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of pathological changes over time. Our findings show a dramatic acceleration and exacerbation of both pathologies. The onset of prion disease symptoms in transgenic mice appeared significantly faster with a concomitant increase on the level of misfolded prion protein in the brain. A striking increase in amyloid plaque deposition was observed in prion-infected mice compared with their noninoculated counterparts. Histological and biochemical studies showed the association of the two misfolded proteins in the brain and in vitro experiments showed that protein misfolding can be enhanced by a cross-seeding mechanism. These results suggest a profound interaction between Alzheimer's and prion pathologies, indicating that one protein misfolding process may be an important risk factor for the development of a second one. Our findings may have important implications to understand the origin and progression of PMDs.

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“…CJD with a point mutation of valine (Val) to isoleucine (Ile) at codon 180 in the PrP gene (V180I CJD) is a type of genetic CJD with no relevant family history 6–14 . V180I CJD is extremely rare in European and North American CJD patients, 3 but it is relatively common in Japanese genetic CJD patients 12 .…”

Section: Introductionmentioning

confidence: 99%

An autopsied case of V180I Creutzfeldt‐Jakob disease presenting with panencephalopathic‐type pathology and a characteristic prion protein type

Iwasaki¹,

Mori²,

Ito³

et al. 2011

Neuropathology

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A 73-year-old Japanese woman showed slowly progressive aphasia, apraxia and dementia. She had no family history of prion disease or dementia. One year later she showed parkinsonism and corticobasal degeneration was initially suspected. On MRI, the left temporal neocortex seemed swollen on T2-weighted images in the initial stage, and a later high-signal intensity region was observed in the cerebral cortex in diffusion-weighted images. The patient developed myoclonus and an akinetic mutism state 15 months and 22 months after onset, respectively. Consecutive electroencephalography revealed no periodic sharp-wave complexes. Prion protein (PrP) gene analysis revealed a valine to isoleucine point mutation at codon 180, and methionine homozygosity at codon 129. This patient's clinical symptoms and disease course were atypical for Creutzfeldt-Jakob disease (CJD), and a stable state with nasal tube-feeding lasted several years. She died of respiratory failure at the age of 81, 102 months after the onset. Autopsy revealed widespread spongiform degeneration with weak synaptic-type PrP deposition, confirming the diagnosis of genetic CJD. Neurons in the cerebral cortex were relatively preserved in number and hypertrophic astrocytosis was generally moderate for such long-term disease, but cerebral white matter showed diffuse severe myelin pallor with tissue rarefaction suggestive of panencephalopatic-type pathology. The cerebellar cortex was relatively well preserved with observation of mild spongiform change in the molecular layer, moderate neuron loss in the Purkinje neuron layer, and scattered small plaque-like PrP deposition. Western blot analysis of protease-resistant PrP showed a characteristic pattern without a diglycoform band. V180I CJD is an interesting form of genetic CJD with regards to the clinicopathologic, molecular and genetic findings.

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An autopsy case of Creutzfeldt-Jakob disease with a V180I mutation of the PrP gene and Alzheimer-type pathology

Cited by 32 publications

References 24 publications

Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene

Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene

Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases

An autopsied case of V180I Creutzfeldt‐Jakob disease presenting with panencephalopathic‐type pathology and a characteristic prion protein type

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