Dorey A, Tholance Y, Vighetto A, Perret-Liaudet A, Lachman I, Krolak-Salmon P, Wagner U, Struyfs H, De Deyn PP, El-Moualij B, Zorzi W, Meyronet D, Streichenberger N, Engelborghs S, Kovacs GG, Quadrio I. Association of cerebrospinal fluid prion protein levels and the distinction between Alzheimer disease and Creutzfeldt-Jakob disease. JAMA Neurol. 2015 Mar;72(3):267-75. PubMed.

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  1. This international study group (Belgium, France, Germany, Austria) retrospectively determined CSF t-PrP and the ratio of total (t)tau and phospho (p)tau 181 in a cohort of 232 patients (30 autopsy-confirmed AD; 52 autopsy-confirmed CJD; 101 probable AD, including 46 atypical AD phenotypes; 26 probable CJD; and 23 non-demented controls). In CJD patients, CSF t-PrP concentrations were decreased compared to controls and AD patients. Differential diagnosis of CJD vs. atypical AD reached 82.1 percent sensitivity and 91.3 percent specificity. Misclassification rate of atypical AD, when using CSF 14-3-3 protein determination alone (43.5 percent) was reduced to 4.3 percent when calculating CSF ratio t-tau / (p-tau181 x t-PrP), with the correct classification reaching 98.4 percent of the patients.

    This study provided evidence that determination of t-PrP in CSF as a new biomarker may help clinicians to exclude CJD in patients with unusual AD phenotype, for whom CJD may be a differential diagnosis, while currently available non-specific biomarkers such as 14-3-3 protein or t-tau diagnostically do not contribute enough. The clinical benefits of using CSR t-PrP in addition to current classic biomarkers should be confirmed by further studies of larger cohorts of confirmed CJD and (atypical) AD patients. 

    View all comments by Kurt A. Jellinger

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