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See detailAssociation of Cerebrospinal Fluid Prion Protein Levels and the Distinction Between Alzheimer Disease and Creutzfeldt-Jakob Disease
Dorey, Aline; Tholance, Yannick; Vighetto, Alain et al

in JAMA Neurology (2015)

IMPORTANCE Although typical forms of Alzheimer disease (AD) and Creutzfeldt-Jakob disease (CJD) are clinically distinguishable, atypical AD phenotypesmay pose a diagnostic challenge. The major biological ... [more ▼]

IMPORTANCE Although typical forms of Alzheimer disease (AD) and Creutzfeldt-Jakob disease (CJD) are clinically distinguishable, atypical AD phenotypesmay pose a diagnostic challenge. The major biological diagnostic biomarker for identifying CJD, 14-3-3 protein in cerebrospinal fluid (CSF), unfortunately lacks specificity when confronting a rapid dementia presentation. OBJECTIVE To assess the relevance of total CSF prion protein (t-PrP) levels in the differential biological diagnosis between atypical AD phenotypes and CJD. DESIGN, SETTING, AND PARTICIPANTS A retrospective study in an autopsy-confirmed cohort of 82 patients was performed to evaluate the relevance of CSF t-PrP to distinguish 30 definite cases of AD from 52 definite cases of CJD. Next, CSF t-PrP concentration was measured in a cohort of 104 patients including 55 patients with probable AD, 26 with probable sporadic CJD, and 23 control patients for whom 14-3-3 protein, total tau, phosphorylated tau 181 (P-tau181), and Aβ1-42 were available.We investigated 46 patients diagnosed as having probable AD who presented atypical phenotypes. A diagnosis strategy was proposed to classify atypical AD phenotypes with suspicion of CJD based on a decision tree combining CSF biomarkers. MAIN OUTCOMES AND MEASURES We determined CSF t-PrP levels for all patients.We calculated the ratio of total tau and P-tau181 and determined the diagnostic accuracy of each biomarker alone or in combination.We calculated the misclassification rate for each biomarker that corresponded to the percentage of patients within the group of atypical AD phenotypes wrongly classified as CJD. RESULTS In patients with CJD, CSF t-PrP concentrations were decreased compared with control participants and patients with AD. When considering the differential diagnosis of CJD compared with atypical AD phenotypes, CSF t-PrP determination reached 82.1%sensitivity and 91.3%specificity. The misclassification rate of atypical AD phenotypes decreased from 43.5%, obtained when using the CSF 14-3-3 protein determination alone, to only 4.3%when calculating the ratio total tau/(P-tau181 × t-PrP). The proposed classification tree permitted correct classification of 98.4%of the patients. CONCLUSIONS AND RELEVANCE For unusual phenotypes of AD, especially cases presenting with a biological ambiguity suggesting CJD, determination of CSF t-PrP levels increased diagnostic accuracy. The use of CSF t-PrP levels may be beneficial in clinical practice in [less ▲]

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See detailCerebrospinal Fluid Collection Tubes: a critical issue for Alzheimer Disease diagnosis
Perret-Liaudet, Armand; Pelpel, Mathieu; Tholance, Yannick et al

in Clinical Chemistry (2012), 58

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