title: Cerebrospinal fluid amyloid-β 42/40 ratio in clinical setting of memory centers: a multicentric study.
abstract: BACKGROUND
  The cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ), tau and phosphorylated tau (p-tau181) are now used for the diagnosis of Alzheimer's disease (AD). Aβ40 is the most abundant Aβ peptide isoform in the CSF, and the Aβ 42/40 ratio has been proposed to better reflect brain amyloid production. However, its additional value in the clinical setting remains uncertain.
  
  
  METHODS
  A total of 367 subjects with cognitive disorders who underwent a lumbar puncture were prospectively included at three French memory centers (Paris-North, Lille and Montpellier; the PLM Study). The frequency of positive, negative and indeterminate CSF profiles were assessed by various methods, and their adequacies with the diagnosis of clinicians were tested using net reclassification improvement (NRI) analyses.
  
  
  RESULTS
  On the basis of local optimum cutoffs for Aβ42 and p-tau181, 22% of the explored patients had indeterminate CSF profiles. The systematic use of Aβ 42/40 ratio instead of Aβ42 levels alone decreased the number of indeterminate profiles (17%; P = 0.03), but it failed to improve the classification of subjects (NRI = -2.1%; P = 0.64). In contrast, the use of Aβ 42/40 ratio instead of Aβ42 levels alone in patients with a discrepancy between p-tau181 and Aβ42 led to a reduction by half of the number of indeterminate profiles (10%; P < 0.001) and was further in agreement with clinician diagnosis (NRI = 10.5%; P = 0.003).
  
  
  CONCLUSIONS
  In patients with a discrepancy between CSF p-tau181 and CSF Aβ42, the assessment of Aβ 42/40 ratio led to a reliable biological conclusion in over 50% of cases that agreed with a clinician's diagnosis.
authors.affiliation: Centre Mémoire Ressources Recherche (CM2R), Paris Nord Ile-de-France, Saint Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, 200 rue du Faubourg Saint-Denis, 75010 Paris, France ; INSERM U942, Biomarkers in CardioNeuroVascular diseases (Bio-CANVAS), University of Paris 7-Denis Diderot, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dumurgier
authors.affiliation: Inserm, UMR 1172, JPArc, Faculté de Médecine, Université de Lille, 59045 Lille, France ; Centre de Biologie-Pathologie, Centre Hospitalier Régional Universitaire, 59037 Lille, France.
authors.forename: Susanna
authors.initials: S
authors.lastname: Schraen
authors.affiliation: Centre Mémoire Ressources Recherche de Montpellier, Université de Montpellier, Montpellier, France ; Biochimie-Protéomique Clinique - IRB - CCBHM, INSERM U1040, Université de Montpellier, Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gabelle
authors.affiliation: Centre Mémoire Ressources Recherche, EA 1046, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vercruysse
authors.affiliation: Centre Mémoire Ressources Recherche, EA 1046, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bombois
authors.affiliation: Service de Biochimie et Biologie Moléculaire, Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: Service de Biochimie et Biologie Moléculaire, Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Katell
authors.initials: K
authors.lastname: Peoc'h
authors.affiliation: Inserm, UMR 1172, JPArc, Faculté de Médecine, Université de Lille, 59045 Lille, France ; Centre de Biologie-Pathologie, Centre Hospitalier Régional Universitaire, 59037 Lille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Sablonnière
authors.affiliation: Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 USA.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Kastanenka
authors.affiliation: Biochimie-Protéomique Clinique - IRB - CCBHM, INSERM U1040, Université de Montpellier, Montpellier, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Delaby
authors.affiliation: Centre Mémoire Ressources Recherche, EA 1046, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.affiliation: Centre Mémoire Ressources Recherche de Montpellier, Université de Montpellier, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Touchon
authors.affiliation: Centre Mémoire Ressources Recherche (CM2R), Paris Nord Ile-de-France, Saint Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, 200 rue du Faubourg Saint-Denis, 75010 Paris, France ; INSERM U942, Biomarkers in CardioNeuroVascular diseases (Bio-CANVAS), University of Paris 7-Denis Diderot, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Hugon
authors.affiliation: Centre Mémoire Ressources Recherche (CM2R), Paris Nord Ile-de-France, Saint Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, 200 rue du Faubourg Saint-Denis, 75010 Paris, France ; INSERM U942, Biomarkers in CardioNeuroVascular diseases (Bio-CANVAS), University of Paris 7-Denis Diderot, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Paquet
authors.affiliation: Biochimie-Protéomique Clinique - IRB - CCBHM, INSERM U1040, Université de Montpellier, Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann