title: Longitudinal stability of cerebrospinal fluid biomarker levels: fulfilled requirement for pharmacodynamic markers in Alzheimer's disease.
abstract: The current treatment for Alzheimer's disease (AD) is purely symptomatic, but medications interfering with underlying pathophysiological processes are being developed. To evaluate a possible disease-modifying effect, cerebrospinal fluid (CSF) biomarkers with a direct link to the underlying pathophysiology, such as amyloid-β(1-42) (Aβ(1-42)), total tau protein (T-tau), and hyperphosphorylated tau (P-tau(181P)), may play an important role. If intra-individual fluctuations in biomarker levels are small, the difference between two samples could serve as a pharmacodynamic measure. The aim of this study was to evaluate the longitudinal stability of CSF Aβ(1-42), T-tau, and P-tau(181P) levels in AD patients and control subjects. Serial CSF samples of 28 AD patients and 23 controls with a minimum time interval of 30 days were included in this study. Serial CSF samples from 10 progressive patients (7 mild cognitive impairment (MCI) patients and 3 controls progressing to MCI or AD) were also analyzed. Intra-individual CSF Aβ(1-42) and P-tau(181P) levels were stable in AD and controls. Intra-individual CSF T-tau levels differed significantly in AD patients, but not in controls. Change in biomarker concentrations per time unit was also significant between groups, but not within groups. The difference in biomarker levels in samples from progressive patients was not significant. In conclusion, CSF levels of Aβ(1-42), T-tau, and P-tau(181P) are relatively stable over time. Only T-tau increased in AD patients in comparison to controls, which does not preclude its use as a diagnostic marker, nor as a potential pharmacodynamic marker.
authors.affiliation: Laboratory of Neurochemistry and Behavior, Reference Center for Biological Markers of Dementia (BIODEM), Antwerp, Belgium. nathalie.lebastard@ua.ac.be
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Bastard
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aerts
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000235:genetics; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D013129:Spinal Puncture; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins