title: Mapping CSF biomarker profiles onto NIA-AA guidelines for Alzheimer's disease.
abstract: The National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines for Alzheimer's disease (AD) propose the categorization of individuals according to their biomarker constellation. Though the NIA-AA criteria for preclinical AD and AD dementia have already been applied in conjunction with imaging AD biomarkers, the application of the criteria using comprehensive cerebrospinal fluid (CSF) biomarker information has not been thoroughly studied yet. The study included a monocentric cohort with healthy (N = 41) and disease (N = 22) controls and patients with AD dementia (N = 119), and a multicentric sample with healthy controls (N = 116) and patients with AD dementia (N = 102). The CSF biomarkers β-amyloid 1-42, total tau, and phosphorylated tau at threonine 181 were measured with commercially available assays. Biomarker values were trichotomized into positive for AD, negative, or borderline. In controls the presence of normal CSF profiles varied between 13.6 and 25.4 % across the studied groups, while up to 8.6 % of them had abnormal CSF biomarkers. In 40.3-52.9 % of patients with AD dementia, a typical CSF profile for AD was detected. Approximately 40 % of the potential biomarker constellations are not considered in the NIA-AA guidelines, and more than 40 % of participants could not be classified into the NIA-AA categories with distinct biomarker constellations. Here, a refined scheme covering all potential biomarker constellations is proposed. These results enrich the discussion on the NIA-AA guidelines and point to a discordance between clinical symptomatology and CSF biomarkers even in patients with full-blown AD dementia, who are supposed to have a clearly positive for AD neurochemical profile.
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. panos.alexopoulos@lrz.tum.de.|Department of Psychiatry, University Hospital of Rion, University of Patras, 26500, Rion, Patras, Greece. panos.alexopoulos@lrz.tum.de.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roesler
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thierjung
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Max Planck Institute of Psychiatry, 80804, Munich, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Werle
authors.affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Buck
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Yakushev
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Gleixner
authors.affiliation: Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kagerbauer
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Ortner
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kübler
authors.affiliation: Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Martin
authors.affiliation: Department of Informatics, Aristotle University of Thessaloniki, Thessaloníki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Laskaris
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Neuroepidemiology and Ageing Research Unit, Faculty of Medicine, School of Public Health, The Imperial College of Science, Technology and Medicine, London, UK.|West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000145:classification; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054561:National Institute on Aging (U.S.) / Q000592:standards*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012955:Societies, Medical / Q000592:standards*; D014481:United States; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Biomarkers; Cognitive aging; Dementia; Diagnostic criteria