Edinburgh Research Explorer Cerebrospinal Fluid Biomarkers in Human Genetic Transmissible Spongiform Encephalopathies

Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. Abstract The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10–15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD.

[1]  P. Johannsen,et al.  The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease , 2009, Neurobiology of Aging.

[2]  J. Molinuevo,et al.  First demonstrated de novo insertion in the prion protein gene in a young patient with dementia , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[3]  K. Hess,et al.  Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosis , 2007, Journal of Neurology.

[4]  J. Collinge,et al.  Novel mutation of the PRNP gene of a clinical CJD case , 2006, BMC infectious diseases.

[5]  K. Hess,et al.  CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease , 2006, Neurology.

[6]  M. Sierra-Moros,et al.  Impact of the clinical context on the 14-3-3 test for the diagnosis of sporadic CJD , 2006, BMC neurology.

[7]  M. Pancorbo,et al.  Phenotypic variability in familial prion diseases due to the D178N mutation , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[8]  A. Aguzzi,et al.  Genetic prion disease: the EUROCJD experience , 2005, Human Genetics.

[9]  P. Cras,et al.  Cerebrospinal fluid biomarkers in Creutzfeldt–Jakob disease , 2005, Clinical Neurology and Neurosurgery.

[10]  M. Equestre,et al.  High incidence of genetic human transmissible spongiform encephalopathies in Italy , 2005, Neurology.

[11]  H. Kretzschmar,et al.  Creutzfeldt-Jakob disease associated with an R148H mutation of the prion protein gene , 2005, Neurogenetics.

[12]  B. Maras,et al.  Creutzfeldt-Jakob disease associated with the R208H mutation in the prion protein gene , 2005, Neurology.

[13]  H. Kretzschmar,et al.  Creutzfeldt-Jakob disease in a patient with an R208H mutation of the prion protein gene (PRNP) and a 17-kDa prion protein fragment , 2005, Acta Neuropathologica.

[14]  J. Yagüe,et al.  Clinical and genetic features of human prion diseases in Catalonia: 1993–2002 , 2004, European journal of neurology.

[15]  J. Martín,et al.  A prospective study of CSF markers in 250 patients with possible Creutzfeldt–Jakob disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[16]  H. Kretzschmar,et al.  [Clinically atypical CJD: diagnostic relevance of cerebrospinal fluid markers and molecular genetic analysis?]. , 2002, Deutsche medizinische Wochenschrift.

[17]  J. Wiltfang,et al.  Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt–Jakob disease , 2002, Neurology.

[18]  R. Nitrini,et al.  Familial Creutzfeldt-Jakob disease associated with a point mutation at codon 210 of the prion protein gene. , 2001, Arquivos de neuro-psiquiatria.

[19]  F. Squitieri,et al.  Mutation of the PRNP gene at codon 211 in familial Creutzfeldt-Jakob disease. , 2001, American journal of medical genetics.

[20]  H. Budka,et al.  Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt–Jakob disease , 2000, Neurology.

[21]  C. Masters,et al.  Novel prion protein gene mutation in an octogenarian with Creutzfeldt-Jakob disease. , 2000, Archives of neurology.

[22]  D. Restivo,et al.  Deafness: an unusual onset of genetic Creutzfeldt-Jakob disease , 2000, Neurological Sciences.

[23]  A. Korczyn,et al.  Preliminary evidence for anticipation in genetic E200K Creutzfeldt-Jakob disease , 1999, Neurology.

[24]  T. Kato,et al.  [Clinicopathological characteristics of Creutzfeldt-Jakob disease with a PrP V180I mutation and M129V polymorphism on different alleles]. , 1999, Rinsho shinkeigaku = Clinical neurology.

[25]  A. Giese,et al.  Phenotypic variability in fatal familial insomnia (D178N-129M) genotype , 1998, Neurology.

[26]  K. Mitsuo,et al.  [Gerstmann-Sträussler-Scheinker syndrome with a Pro102Leu mutation in the prion protein gene and atypical MRI findings, hyperthermia, tachycardia, and hyperhidrosis]. , 1998, Rinsho shinkeigaku = Clinical neurology.

[27]  R. Petersen,et al.  Prion encephalopathy with insertion of octapeptide repeats: the number of repeats determines the type of cerebellar deposits , 1998, Neuropathology and applied neurobiology.

[28]  J. Chapman,et al.  Identification in Israel of 2 Jewish Creutzfeldt — Jakob disease patients with a 178 mutation at their PrP gene , 1998, Acta neurologica Scandinavica.

[29]  Trey Sunderland,et al.  Decreased-Amyloid 1-42 and Increased Tau Levels in Cerebrospinal Fluid of Patients With Alzheimer Disease , 2003 .

[30]  H. Budka,et al.  Mutations of the prion protein gene phenotypic spectrum. , 2002, Journal of neurology.