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However, this assay cannot be used for screening because of the high rate of false positive results in sCJD, and often negative results in variant CJD. To facilitate the differential diagnosis of CJD, we applied 2\u2010D differential gel\u2010electrophoresis (2\u2010D DIGE) as a quantitative proteomic screening system for CSF proteins. We compared 36 patients suffering from sCJD with 30 patients suffering from other neurodegenerative diseases. Sample preparation was optimized in consideration of the fact that CSF is composed of blood\u2010 and brain\u2010derived proteins, and an improved 2\u2010D DIGE protocol was established. Using this method in combination with protein identification by MALDI\u2010TOF\u2010MS, several known surrogate markers of sCJD like 14\u20103\u20103 protein, neuron\u2010specific enolase, and lactate dehydrogenase were readily identified. Moreover, a not yet identified protein with an approximate molecular mass of 85\u2005kDa was found as marker for sCJD with high diagnostic specificity and sensitivity. We conclude that our proteomic approach is useful to differentiate CJD from other neurodegenerative diseases and expect that CSF\u2010optimized 2\u2010D DIGE will find broad application in the search for other brain derived proteins in CSF.<\/jats:p>","DOI":"10.1002\/pmic.200800375","type":"journal-article","created":{"date-parts":[[2008,9,22]],"date-time":"2008-09-22T09:56:21Z","timestamp":1222077381000},"page":"4357-4366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Cerebrospinal fluid\u2010optimized two\u2010dimensional difference gel electrophoresis (2\u2010D DIGE) facilitates the differential diagnosis of Creutzfeldt\u2013Jakob 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