Impact of the 2008–2012 French Alzheimer Plan on the Use of Cerebrospinal Fluid Biomarkers in Research Memory Center: The PLM Study

Article type: Research Article

Authors: Gabelle, Audrey^{a; b; 1; *} | Dumurgier, Julien^{c; 1} | Vercruysse, Olivier^{d; 1} | Paquet, Claire^{c; e} | Bombois, Stéphanie^d | Laplanche, Jean-Louis^f | Peoc'h, Katell^f | Schraen, Susanna^g | Buée, Luc^g | Pasquier, Florence^d | Hugon, Jacques^{c; e} | Touchon, Jacques^{a; h} | Lehmann, Sylvain^b

Affiliations: [a] Centre Mémoire Ressources Recherche Languedoc-Roussillon, CHU de Montpellier, hôpital Gui de Chauliac, Montpellier, and Université Montpellier I, Montpellier, France | [b] Biochimie-Protéomique Clinique – IRB – CCBHM – Inserm U1040 CHU de Montpellier, Montpellier, France | [c] Centre Mémoire Ressources Recherche Paris Nord Ile-de-France, hôpital Saint Louis – Lariboisière – Fernand Widal Hospital, AP-HP, Université Paris 7-Denis Diderot, Paris, France | [d] Centre Mémoire Ressources Recherche Lille, CHU de Lille, EA 1046, Université Lille-Nord de France, Lille, France | [e] Institut du Fer à Moulin, INSERM U839, Paris, France | [f] Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, APHP – Inserm U705/UMR8206, Paris, France | [g] CHU de Lille, Centre de Biologie Pathologie, Université Lille-Nord de France, INSERM U837, Lille, France | [h] INSERM U1061, Hôpital la Colombière, CHU de Montpellier, Montpellier, France

Correspondence: [*] Correspondence to: Dr. Audrey Gabelle, Centre Mémoire Ressources Recherche (CMRR) Montpellier, Hôpital Gui de Chauliac, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France. E-mail: [email protected].

Note: [1] These authors contributed equally to the manuscript.

Abstract: The French Alzheimer's Disease Plan aims, in an unprecedented national effort, to develop research, promote optimal diagnosis, and take better care of patients. In order to evaluate the clinical interest and use of cerebrospinal fluid (CSF) biomarkers, a data-sharing project, the PLM (Paris-North, Lille and Montpellier) study has emerged through collaboration between these memory centers, already involved in this field. The revised Alzheimer's disease (AD) diagnosis criteria include CSF biomarkers, but little is known about their use in routine clinical practice. To evaluate their interest and diagnostic accuracy in routine AD diagnosis, a cohort of 677 patients from Montpellier was first analyzed. The results were then validated through the analysis of a second cohort of 638 patients from Lille and Paris-Nord. Diagnoses of AD and other dementias were established by multidisciplinary expert teams, based on neuropsychological exams and structural brain imaging, blinded from CSF results. CSF amyloid-β, tau, and p-tau concentrations were measured for all patients. Receiver-operating characteristic curves were used to define cut-offs and evaluate the ability of each biomarker to discriminate AD from other diagnoses. We showed that p-tau outperformed other biomarkers for discriminating AD from non-AD patients and presents a clear clinical interest. The other biomarkers also showed relevant variations especially when the differential AD diagnoses were taken into account. Altogether we could demonstrate in both mono-centric and multi-centric cohorts from memory clinics the capacity of CSF biomarkers to discriminate AD from non-AD patients in clinical routine with a high sensitivity and specificity.

Keywords: Alzheimer's disease, amyloid-β peptides, cerebrospinal fluid biomarkers, cohort studies, dementia, p-tau

DOI: 10.3233/JAD-121549

Journal: Journal of Alzheimer's Disease, vol. 34, no. 1, pp. 297-305, 2013