S Lehmann1, C Paquet2, C Malaplate-Armand3, E Magnin4, S Schraen5, M Quillard-Muraine6, O Bousiges7, C Delaby1, J Dumurgier2, J Hugon2, B Sablonnière4, F Blanc8, D Wallon9, A Gabelle10, J L Laplanche11, E Bouaziz-Amar11, K Peoc'h12. 1. CHU de Montpellier and Université de Montpellier, IRMB, CRB, Laboratoire de Biochimie et Protéomique Clinique, 80 Avenue Augustin Fliche, 34295 Montpellier, France. 2. Centre de Neurologie Cognitive, Groupe Hospitalier Saint-Louis Lariboisière Fernand-Widal APHP, INSERM U942, Université Paris Diderot, France. 3. Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie - Endocrinologie - Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France. 4. Centre Mémoire Ressources Recherche Besançon Franche-Comté, Departement of Neurology, CHU Besançon, Besançon, France. 5. Univ.Lille, Inserm, CHU-Lille, UMR-S1172 and Neurobiology Unit, Centre de Biologie-Pathologie, Lille, France. 6. Laboratoire de Biochimie, Rouen University Hospital, Rouen, France. 7. Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital de Hautepierre, Hôpitaux Universitaire de Strasbourg, Strasbourg, France; Laboratoire de Neurosciences cognitives et Adaptatives (LNCA), UMR7364 Unistra/CNRS, Strasbourg, France. 8. 2ICube laboratory and FMTS (Fédération de Médecine Translationnelle de Strasbourg), team IMIS-Neurocrypto, University of Strasbourg and CNRS, Strasbourg, France. 9. Inserm U1079, University of Rouen, Department of Neurology, France. 10. Centre Mémoire Ressources Recherche, CHU de Montpellier, Hôpital Gui de Chauliac, Montpellier, Université Montpellier, Montpellier, France. 11. Service de Biochimie et Biologie moléculaire, GH Saint-Louis-Lariboisière-Fernand Widal, APHP, Paris, France. 12. Service de Biochimie et Biologie moléculaire, GH Saint-Louis-Lariboisière-Fernand Widal, APHP, Paris, France; APHP, HUPNVS, Hôpital Beaujon, Biochimie clinique, Clichy, France; Université Paris Diderot, France. Electronic address: Katell.peoch@aphp.fr.
Abstract
CONTEXT: Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling. PATIENTS AND METHODS: Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and Aβ 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis. RESULTS: Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creuztfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/ central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, Aβ1-42 and Aβ1-42/pTau values differed significantly between the three groups of patients (p < .001). An Aβ1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creuztfeldt-Jakob disease in case of Aβ1-42 concentrations <550 pg/mL or pTau>60 pg/mL. CONCLUSION: This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF.
CONTEXT: Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling. PATIENTS AND METHODS: Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and Aβ 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis. RESULTS: Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creuztfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/ central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, Aβ1-42 and Aβ1-42/pTau values differed significantly between the three groups of patients (p < .001). An Aβ1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creuztfeldt-Jakob disease in case of Aβ1-42 concentrations <550 pg/mL or pTau>60 pg/mL. CONCLUSION: This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF.
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