title: Effect of human cerebrospinal fluid sampling frequency on amyloid-β levels.
abstract: BACKGROUND
  β-amyloid peptide (Aβ) is associated with neurodegeneration in Alzheimer's disease. Emerging evidence indicates that Aβ levels in cerebrospinal fluid (CSF) may serve as an early clinical biomarker for evaluating pharmacological activity of new drug candidates targeting Aβ production or Aβ clearance. Therefore, it is critical to understand whether intrasubject levels of CSF Aβ are consistent between sampling intervals to determine whether Aβ can be used as a pharmacodynamic biomarker for drug candidates. Previous studies have produced seemingly conflicting observations for the intrasubject stability of CSF Aβ levels; we attempt to reconcile these conflicting observations.
  
  
  METHODS
  The current study examined the Aβ 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 Aβ levels, and that lowering the CSF sampling frequency may help minimize this effect.
  
  
  CONCLUSIONS
  These results will help guide clinical trial design for Alzheimer's disease therapy.
authors: Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park, IL, USA. jinhe.li@abbott.com
authors: Jinhe
authors: J
authors: Li
authors: Daniel A
authors: DA
authors: Llano
authors: Teresa
authors: T
authors: Ellis
authors: David
authors: D
authors: LeBlond
authors: Anahita
authors: A
authors: Bhathena
authors: Stanford S
authors: SS
authors: Jhee
authors: Larry
authors: L
authors: Ereshefsky
authors: Robert
authors: R
authors: Lenz
authors: Jeffrey F
authors: JF
authors: Waring
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments