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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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See detailRisk of Alzheimer’s Disease biological misdiagnosis linked to cerebrospinal collection tubes
Perret-Liaudet, Armand; Pelpel, Mathieu; Tholance, Yannick et al

in Journal of Alzheimer's Disease [=JAD] (2012), 31((1)), 13-20

Tau proteins and amyloid-β (Aβ) peptides are the current recognized cerebrospinal fluid (CSF) biomarkers used as an aid in the diagnosis of Alzheimer's disease (AD). However, there is no consensus on ... [more ▼]

Tau proteins and amyloid-β (Aβ) peptides are the current recognized cerebrospinal fluid (CSF) biomarkers used as an aid in the diagnosis of Alzheimer's disease (AD). However, there is no consensus on their clinical use due to non-qualified cut-off values, probably related to the observed high pre-analytical and analytical variability. Standardized pre-analytical protocols have therefore been proposed. Importantly, these recommend the use of polypropylene collection/sampling tubes while, to date, no broad comparison of these types of tubes has been conducted. In this study, we first compared, as part of a real clinical workflow, the impact of four different collection tubes on the CSF concentration of Aβ peptides (Aβ42, Aβ40) and total (hTau) and phosphorylated (P-Tau181P) tau proteins measured using routine ELISA kits. We then extended this study to 11 polypropylene tubes used by different clinical laboratories, and investigated their plastic polymer composition using differential scanning calorimetry and Fourier Transformed Infrared spectroscopy. Significant concentration variations linked solely to the use of different types of tubes were observed. This was particularly marked for Aβ peptides, with >50% disparity occurring in less than five minutes. Polymer composition analysis revealed that most polypropylene tubes were in fact copolymers with at least polyethylene. There was no clear correlation between tube composition and pre-analytical behavior. Our results show that the use of polypropylene tubes does not guarantee satisfactory pre-analytical behavior. They also point to collection/sampling tubes being a major pre-analytical source of variability that could impact the significance of AD biological diagnosis. [less ▲]

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