title: Conflicting cerebrospinal fluid biomarkers and progression to dementia due to Alzheimer's disease.
abstract: According to new diagnostic guidelines for Alzheimer's disease (AD), biomarkers enable estimation of the individual likelihood of underlying AD pathophysiology and the associated risk of progression to AD dementia for patients with mild cognitive impairment (MCI). Nonetheless, how conflicting biomarker constellations affect the progression risk is still elusive. The present study explored the impact of different cerebrospinal fluid (CSF) biomarker constellations on the progression risk of MCI patients.
  
  
  
  A multicentre cohort of 469 patients with MCI and available CSF biomarker results and clinical follow-up data was considered. Biomarker values were categorized as positive for AD, negative or borderline. Progression risk differences between patients with different constellations of total Tau (t-Tau), phosphorylated Tau at threonine 181 (p-Tau) and amyloid-beta 1-42 (Aβ42) were studied. Group comparison analyses and Cox regression models were employed.
  
  
  
  Patients with all biomarkers positive for AD (N = 145) had the highest hazard for progression to dementia due to AD, whilst patients with no positive biomarkers (N = 111) had the lowest. The risk of patients with only abnormal p-Tau and/or t-Tau (N = 49) or with positive Aβ42in combination with positive t-Tau or p-Tau (N = 119) is significantly lower than that of patients with all biomarkers positive.
  
  
  
  The risk of progression to dementia due to AD differs between patients with different CSF biomarker constellations.
authors.affiliation: Department of Psychiatry, University Hospital of Rion, University of Patras, 26504, Rio, Patras, Greece. panos.alexopoulos@upatras.gr.|Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany. panos.alexopoulos@upatras.gr.|Department of Psychiatry, University Hospital of Patras, University of Patras, 26504, Rion, Patras, Greece. panos.alexopoulos@upatras.gr.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, München, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Werle
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roesler
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thierjung
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany.
authors.forename: Lena Sophie
authors.initials: LS
authors.lastname: Gleixner
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Yakushev
authors.affiliation: Department of Informatics, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Laskaris
authors.affiliation: Institute of Medical Biometrics, Epidemiology, and Medical Informatics (IMBEI), University of the Saarland, 66421, Homburg/Saar, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.affiliation: Department of Psychiatry, University Hospital of Rion, University of Patras, 26504, Rio, Patras, Greece.
authors.forename: Philippos
authors.initials: P
authors.lastname: Gourzis
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany.|Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, W6 8RP, UK.|Department of Psychiatry and Psychotherapy, Ludwig-Maximilans-Universität München, Nußbaumstraße 7, München, 80336, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000209:etiology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016016:Proportional Hazards Models; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; Cerebrospinal fluid; Mild cognitive impairment; Prognosis