Article (Scientific journals)
Association of Cerebrospinal Fluid Prion Protein Levels and the Distinction Between Alzheimer Disease and Creutzfeldt-Jakob Disease
Dorey, Aline; Tholance, Yannick; Vighetto, Alain et al.
2015In JAMA Neurology, p. 1-9
Peer Reviewed verified by ORBi
 

Files


Full Text
Neuroscren noi140104.pdf
Publisher postprint (383.03 kB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Alzheimer; CJD; CSF
Abstract :
[en] 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
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Dorey, Aline
Tholance, Yannick
Vighetto, Alain
Perret-Liaudet, Armand
Lachman, Ingolf
Krolak-Salmon, Pierre
Wagner, Uta
Stuyfs, Hanne
De Deyn, Peter
Elmoualij, Benaïssa ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie
Zorzi, Willy ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie
Meyronet, David
Streichenberger, Nathalie
Engelborghs, Sebastiaan
Kovacs, Gabor G
Quadrio, Isabelle
More authors (6 more) Less
Language :
English
Title :
Association of Cerebrospinal Fluid Prion Protein Levels and the Distinction Between Alzheimer Disease and Creutzfeldt-Jakob Disease
Publication date :
05 January 2015
Journal title :
JAMA Neurology
ISSN :
2168-6149
eISSN :
2168-6157
Publisher :
American Medical Association, Chicago, United States - Illinois
Pages :
1-9
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
NEUROSCREEN, EU FP6, LSHB-CZ-2006-037719
Available on ORBi :
since 20 January 2015

Statistics


Number of views
78 (16 by ULiège)
Number of downloads
4 (3 by ULiège)

Scopus citations®
 
62
Scopus citations®
without self-citations
53
OpenCitations
 
56

Bibliography


Similar publications



Contact ORBi