title: Longitudinal changes of CSF biomarkers in memory clinic patients.
abstract: OBJECTIVE
  In Alzheimer disease (AD), longitudinal changes of beta-amyloid(1-42) (Abeta(1-42)), tau, and phosphorylated tau at threonine 181 (ptau-181) in CSF have been reported in small studies only. We evaluated the natural course of CSF biomarkers in patients with AD, subjective complaints, and mild cognitive impairment (MCI).
  
  
  METHODS
  One hundred five patients (50 AD, 38 MCI, 17 subjective complaints) underwent two lumbar punctures, with a mean interval of 21 +/- 9 months. CSF levels of Abeta(1-42), tau, and ptau-181 were measured.
  
  
  RESULTS
  CSF Abeta(1-42) and tau levels showed main effects for both diagnosis and time (all p < 0.05), with average increases of 47 +/- 72 and 49 +/- 143 pg/mL. The interaction terms were not significant, which implies a similar time effect for all diagnostic groups. CSF ptau-181 levels showed a main effect for diagnosis (p = 0.01) but not for time (p = 0.27, increase of 1.0 +/- 12 pg/mL).
  
  
  CONCLUSIONS
  Levels of CSF beta-amyloid(1-42) and tau but not phosphorylated tau at threonine 181 increased over time in this memory clinic patient cohort with comparable change in all diagnostic groups. The cross-sectional difference between diagnostic groups, however, exceeded by far the longitudinal changes within individuals, suggesting that these biomarkers are not sensitive as markers of disease progression.
authors.affiliation: Alzheimer Center and Department of Neurology, VU Medical Center, Amsterdam, The Netherlands. femke.bouwman@vumc.nl
authors.forename: F H
authors.initials: FH
authors.lastname: Bouwman
authors.forename: W M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: N S M
authors.initials: NS
authors.lastname: Schoonenboom
authors.forename: E J
authors.initials: EJ
authors.lastname: van Elk
authors.forename: A
authors.initials: A
authors.lastname: Kok
authors.forename: F
authors.initials: F
authors.lastname: Rijmen
authors.forename: M A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: P
authors.initials: P
authors.lastname: Scheltens
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D010044:Outpatient Clinics, Hospital / Q000639:trends*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid