Effect of human cerebrospinal fluid sampling frequency on amyloid-ß levels.

ABSTRACT

BACKGROUND: ß-amyloid peptide (Aß) is associated with neurodegeneration in Alzheimer's disease. Emerging evidence indicates that Aß levels in cerebrospinal fluid (CSF) may serve as an early clinical biomarker for evaluating pharmacological activity of new drug candidates targeting Aß production or Aß clearance. Therefore, it is critical to understand whether intrasubject levels of CSF Aß are consistent between sampling intervals to determine whether Aß can be used as a pharmacodynamic biomarker for drug candidates. Previous studies have produced seemingly conflicting observations for the intrasubject stability of CSF Aß levels; we attempt to reconcile these conflicting observations. METHODS: The current study examined the Aß levels in CSF collected with various sampling frequencies from three clinical studies conducted in healthy young or elderly subjects at the same investigative site for the purpose of designing future studies. RESULTS: The results suggest that CSF sampling frequency and/or sampling volume contributes to intrasubject variability in CSF Aß levels, and that lowering the CSF sampling frequency may help minimize this effect. CONCLUSION: These results will help guide clinical trial design for Alzheimer's disease therapy.