Method for the determination of the levels of beta-amyloid peptide in the CSF sampled from freely moving rats.
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.
El Mouedden
Mohammed
M
Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium. melmoued@PRDBE.jnj.com
Haseldonckx
Marc
M
Mackie
Claire
C
Meert
Theo
T
Mercken
Marc
M
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
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