Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

被引：0

作者：

Ellen Gelpi

Simone Baiardi

Carlos Nos

Sofia Dellavalle

Iban Aldecoa

Raquel Ruiz-Garcia

Lourdes Ispierto

Domingo Escudero

Virgina Casado

Elena Barranco

Anuncia Boltes

Laura Molina-Porcel

Nuria Bargalló

Marcello Rossi

Angela Mammana

Dorina Tiple

Luana Vaianella

Elisabeth Stoegmann

Ingrid Simonitsch-Klupp

Gregor Kasprian

Sigrid Klotz

Romana Höftberger

Herbert Budka

Gabor G. Kovacs

Isidre Ferrer

Sabina Capellari

Raquel Sanchez-Valle

Piero Parchi

机构：

[1] Medical University of Vienna and Austrian Reference Center for Human Prion Diseases (ÖRPE),Division of Neuropathology and Neurochemistry, Department of Neurology

[2] Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS,Department of Biomedical and Neuromotor Sciences (DIBINEM)

[3] IRCCS Istituto delle Scienze Neurologiche di Bologna,Department of Pathology, Center for Biomedical Diagnosis

[4] University of Bologna,Department of Immunology, Center for Biomedical Diagnosis

[5] General Subdirectorate of Surveillance and Response to Emergencies in Public Health,Cognitive and Movement Disorders Unit

[6] Department of Public Health in Catalonia,Neurology Department

[7] Hospital Clinic de Barcelona,Department of Geriatrics

[8] University of Barcelona,Department of Neurology

[9] Hospital Clinic de Barcelona,Neurology Department, Alzheimer Disease and Other Cognitive Disorders Unit

[10] Hospital Germans Trias I Pujol de Badalona,Radiology Department, Image Diagnosis Center

[11] Hospital de Mataró,Department of Neuroscience

[12] Hospital General de Granollers,Department of Neurology

[13] Hospital General de Granollers,Department of Pathology

[14] Hospital Clinic de Barcelona,Department of Biomedical Imaging and Image

[15] Hospital Clínic de Barcelona,Guided Therapy

[16] Spain and Magnetic Resonance Image Core Facility of IDIBAPS,Tanz Centre for Research in Neurodegenerative Disease

[17] Istituto Superiore di Sanità,Department of Laboratory Medicine and Pathobiology and Department of Medicine

[18] Medical University of Vienna,Laboratory Medicine Program & Krembil Brain Institute

[19] Medical University of Vienna,Department of Pathology and Experimental Therapeutics

[20] Medical University of Vienna,undefined

[21] University of Toronto,undefined

[22] University of Toronto,undefined

[23] University Health Network,undefined

[24] University of BarcelonaBellvitge University Hospital-IDIBELLCIBERNED,undefined

来源：

Acta Neuropathologica Communications | / 10卷

关键词：

CJD; PrP; Prion disease; Histotype; Classification; Prion strains; Codon 129;

D O I：

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中图分类号：

学科分类号：

摘要：

The methionine (M)—valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype.

引用

共 166 条

[1]

Aguzzi A(2007)Insights into prion strains and neurotoxicity Nat Rev Mol Cell Biol 8 552-561

[2]

Heikenwalder M(2021)Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study Acta Neuropathol 141 159-172

[3]

Polymenidou M(2019)Recent advances in the histo-molecular pathology of human prion disease Brain Pathol 29 278-300

[4]

Attems J(2021)Phenotypic diversity of genetic Creutzfeldt-Jakob disease: a histo-molecular-based classification Acta Neuropathol 142 707-728

[5]

Toledo JB(2021)Environmental and host factors that contribute to prion strain evolution Acta Neuropathol 142 5-16

[6]

Walker L(1994)Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy J Virol 68 7859-7868

[7]

Gelpi E(2010)Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties Proc Natl Acad Sci U S A 107 12005-12010

[8]

Gentleman S(2020)Co-existence of PrP Sci Rep 10 1503-766

[9]

Halliday G(2014) types 1 and 2 in sporadic Creutzfeldt-Jakob disease of the VV subgroup: phenotypic and prion protein characteristics Acta Neuropathol 128 755-708

[10]

Baiardi S(2008)Primary age-related tauopathy (PART): a common pathology associated with human aging Ann Neurol 63 697-360

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