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.2005.02.002 | DOI Listing |
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