K Gmitterová1,2, U Heinemann1, A Krasnianski1,3, J Gawinecka1,4, I Zerr1. 1. Department of Neurology, Clinical Dementia Centre and DZNE, University Medical School, Georg-August University, Göttingen, Germany. 2. Second Department of Neurology, Comenius University, Bratislava, Slovakia. 3. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany. 4. Institute for Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
Abstract
BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. METHODS: The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. RESULTS: Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P < 0.001) and NSE (P = 0.03) was observed in VV2 compared to VV1 subtype. PRNP codon 129 genotype, PrP(sc) isotype, disease duration and clinical stage influenced the test sensitivity in all proteins. CONCLUSIONS: Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known.
BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. METHODS: The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. RESULTS: Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P < 0.001) and NSE (P = 0.03) was observed in VV2 compared to VV1 subtype. PRNP codon 129 genotype, PrP(sc) isotype, disease duration and clinical stage influenced the test sensitivity in all proteins. CONCLUSIONS: Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known.
Authors: Piotr Lewczuk; Peter Riederer; Sid E O'Bryant; Marcel M Verbeek; Bruno Dubois; Pieter Jelle Visser; Kurt A Jellinger; Sebastiaan Engelborghs; Alfredo Ramirez; Lucilla Parnetti; Clifford R Jack; Charlotte E Teunissen; Harald Hampel; Alberto Lleó; Frank Jessen; Lidia Glodzik; Mony J de Leon; Anne M Fagan; José Luis Molinuevo; Willemijn J Jansen; Bengt Winblad; Leslie M Shaw; Ulf Andreasson; Markus Otto; Brit Mollenhauer; Jens Wiltfang; Martin R Turner; Inga Zerr; Ron Handels; Alexander G Thompson; Gunilla Johansson; Natalia Ermann; John Q Trojanowski; Ilker Karaca; Holger Wagner; Patrick Oeckl; Linda van Waalwijk van Doorn; Maria Bjerke; Dimitrios Kapogiannis; H Bea Kuiperij; Lucia Farotti; Yi Li; Brian A Gordon; Stéphane Epelbaum; Stephanie J B Vos; Catharina J M Klijn; William E Van Nostrand; Carolina Minguillon; Matthias Schmitz; Carla Gallo; Andrea Lopez Mato; Florence Thibaut; Simone Lista; Daniel Alcolea; Henrik Zetterberg; Kaj Blennow; Johannes Kornhuber Journal: World J Biol Psychiatry Date: 2017-10-27 Impact factor: 4.132