Method for the determination of the levels of beta-amyloid peptide in the CSF sampled from freely moving rats.

J Pharmacol Toxicol Methods

Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium.

Published: June 2006

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.

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http://dx.doi.org/10.1016/j.vascn.2005.02.002DOI Listing

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