INTRODUCTION: 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. DISCUSSION: 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.
INTRODUCTION: 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. DISCUSSION: 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: Leon M Tai; Helmut Jacobsen; Laurence Ozmen; Alexander Flohr; Roland Jakob-Roetne; Antonello Caruso; Hans-Peter Grimm Journal: J Pharmacokinet Pharmacodyn Date: 2012-04-06 Impact factor: 2.745