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Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

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Abstract

The clinical diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and β amyloid (Aβ42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Aβ42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b—93/93%, t-tau—93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Aβ42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD.

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Acknowledgments

The authors thank the Portuguese Surveillance Group for Human Prion Diseases, its coordinator and José Cortez Pimentel (Hospital de Sta. Maria, Lisbon) for support and implementation of the study. We are grateful to Alison Green (National CJD Surveillance Unit, University of Edinburgh) for scientific advice, Manuela Grazina, Filipe Silva (Department of Biochemistry, Faculty of Medicine, Universidade de Coimbra), Pedro Loureiro and Conceição Silva (Genetics Department, National Institute of Health Dr. Ricardo Jorge, Lisbon) for technical assistance and Gil Cunha (Center for Neuroscience and Cell Biology, PDBEB, University of Coimbra) for reviewing the MRI reports. We also wish to thank all the physicians who sent us the CSF and brain samples and clinical and neuropathological information on suspected CJD cases: Isabel Santana (Hospitais da Universidade de Coimbra), Álvaro Machado (Hospital de S. Marcos, Braga), Grilo Gonçalves (Centro Hospitalar de Coimbra), Miguel Veloso (Hospital de S. Miguel, Oliveira de Azeméis), Edmeia Monteiro (Hospital do Barlavento Algarvio, Portimão), Alfredo de Sá (Hospital S. André, Leiria) Carolina Garrett (Hosp S. João, Porto) Dílio Alves (Hospital Pedro Hispano, Matosinhos) José Pimentel (Hospital Sta. Maria, Lisbon) Isabel Carmo (Hospital Egas Moniz, Lisbon), Rita Almeida (Hospital S. António dos Capuchos, Lisbon), Bastos Lima (Hospital S. António, Porto), Joaquim Machado Cândido (Hosp S. José, Lisbon) Elia Baeta (Centro Hospitalar Alto Minho, Viana do Castelo) and Miguel Viana Baptista (Hospital Garcia de Orta, Lisbon).

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Baldeiras, I.E., Ribeiro, M.H., Pacheco, P. et al. Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients. J Neurol 256, 1540–1550 (2009). https://doi.org/10.1007/s00415-009-5160-0

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