title: Decreased sAβPPβ, Aβ38, and Aβ40 cerebrospinal fluid levels in frontotemporal dementia.
abstract: To improve the etiological diagnosis of neurodegenerative dementias like Alzheimer's disease (AD) or frontotemporal dementia (FTD), we evaluated the value of individual and combined measurements of the following relevant cerebrospinal fluid (CSF) biomarkers: Tau, 181p-Tau, Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. This study conducted in two centers included patients with FTD (n = 34), AD (n = 52), as well as a control group of persons without dementia (CTRL, n = 42). Identical clinical criteria and pre-analytical conditions were used while CSF biomarkers were measured using commercial single and multiplex quantitative immunoassays. Thorough statistical analyses, including ROC curves, logistic regressions, and decision trees, were performed. We validated in AD the specific increase of p-Tau levels and the decrease of Aβ42 levels, two biological hallmarks of this disease. Tau concentrations were highest in AD and intermediate in FTD when compared to CTRL. The most interesting results were obtained by focusing on amyloid biomarkers as we found out in FTD a significant decrease of sAβPPβ, Aβ38, and Aβ40 levels. Aβ38 in particular was the most useful biomarker to differentiate FTD subjects from the CTRL population. Combining p-Tau and Aβ38 led us to correctly classifying FTD patients with sensitivity at 85% and specificity at 82%. Significant changes in amyloid biomarkers, particularly for Aβ38, are therefore seen in FTD. This could be quite useful for diagnosis purposes and it might provide additional evidence on the interrelationship between Tau and AβPP biology which understanding is essential to progress towards optimal therapeutic and diagnostic approaches of dementia.
authors.affiliation: Centre Mémoire Ressources Recherche Montpellier, Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, Montpellier cedex 5, France. a-gabelle@chu-montpellier.fr
authors.forename: Audrey
authors.initials: A
authors.lastname: Gabelle
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roche
authors.forename: Christian
authors.initials: C
authors.lastname: Gény
authors.forename: Karim
authors.initials: K
authors.lastname: Bennys
authors.forename: Pierre
authors.initials: P
authors.lastname: Labauge
authors.forename: Yannick
authors.initials: Y
authors.lastname: Tholance
authors.forename: Isabelle
authors.initials: I
authors.lastname: Quadrio
authors.forename: Laurent
authors.initials: L
authors.lastname: Tiers
authors.forename: Baptiste
authors.initials: B
authors.lastname: Gor
authors.forename: Justine
authors.initials: J
authors.lastname: Boulanghien
authors.forename: Chloé
authors.initials: C
authors.lastname: Chaulet
authors.forename: Alain
authors.initials: A
authors.lastname: Vighetto
authors.forename: Bernard
authors.initials: B
authors.lastname: Croisile
authors.forename: Pierre
authors.initials: P
authors.lastname: Krolak-Salmon
authors.forename: Armand
authors.initials: A
authors.lastname: Perret-Liaudet
authors.forename: Jacques
authors.initials: J
authors.lastname: Touchon
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005189:False Positive Reactions; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid* / Q000523:psychology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012372:ROC Curve; D013129:Spinal Puncture; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); C078592:amyloid beta-protein (1-40); D016875:tau Proteins