title: Method for the determination of the levels of beta-amyloid peptide in the CSF sampled from freely moving rats.
abstract: BACKGROUND
  In the present study, a model was developed to determine the effect of secretase inhibition on beta-amyloid peptide (Abeta) levels in the cerebrospinal fluid (CSF) of freely moving adult rats.
  
  
  METHODS
  Rats were chronically implanted with a cannula into the cisterna magna and CSF samples were collected at different time points from the same animal without anaesthesia. The levels of CSF Abeta were measured by a sandwich ELISA assay.
  
  
  RESULTS
  Administration of DAPT, a functional gamma-secretase inhibitor, resulted in a substantial reduction of Abeta40 and Abeta42, confirming the in vivo functionality of the CSF as a biomarker source for endogenous APP processing modulation by secretase inhibitors.
  
  
  CONCLUSIONS
  Thus, the present work provides clear evidence for the usefulness of CSF sampling from the freely moving rat model for testing the effectiveness of small molecule inhibitors of Abeta production.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium. melmoued@PRDBE.jnj.com
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Mouedden
authors.forename: Marc
authors.initials: M
authors.lastname: Haseldonckx
authors.forename: Claire
authors.initials: C
authors.lastname: Mackie
authors.forename: Theo
authors.initials: T
authors.lastname: Meert
authors.forename: Marc
authors.initials: M
authors.lastname: Mercken
mesh_terms: D000284:Administration, Oral; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002624:Chemistry, Clinical / Q000379:methods; D010450:Endopeptidases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D009068:Movement / Q000502:physiology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014280:Triglycerides / Q000008:administration & dosage / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D014280:Triglycerides; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D005680:gamma-Aminobutyric Acid; C057077:1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases