Biomarkers provide crucial guidance to evaluation of disease progression and therapeutic intervention, both in preclinical proof-of-concept studies as for (their translation to) clinical studies. Serial CSF draws, allowing evaluation of baseline levels and their individual evolutions, are of particular interest in this context.
At reMYND, we can offer a number of interesting CSF biomarkers, showing an evolution with age that parallels the one seen in Alzheimer patients. In CSF from these patients, a decrease in Abeta42, increases in total tau and hyperphosphorylated tau, as well as an increase in oligomeric Abeta levels are observed, though the mechanisms responsible for these changes are still not fully understood. reMYND’s APP and TAU transgenics model the postulated changes, as depicted below for CSF Abeta42 in APP-London and CSF pan-tau in hTAU[P301L] and here CSF oligomeric Abeta in APP-London.
We have technically implemented and are currently validating the practice of serial CSF sampling in individual mice, by consecutive cisterna magna punctures* (see pictures below). The potential advantage of applying this technique in preclinical studies, in combination with our established Abeta and tau ELISA’s, is many-fold. Serial CSF draws offer the ability to control the confounding effect of between-mouse variability in Abeta or tau levels. Baseline measurements can assist to compose a more uniform population at study start, and terminal follow-up measurements allow for detecting subtle therapeutic effects at the level of individual mice. Ongoing efforts are exploring the feasibility of more frequent serial CSF drawings, rendering it possible to monitor therapeutic effects on CSF biomarkers over time within the context of more chronical studies.
* Our method is largely based on the one described in the following paper of Karen Duff and co-workers: Liu L, Duff K. A Technique for Serial Collection of Cerebrospinal Fluid from the Cisterna Magna in Mouse. J Vis Exp. 21 (2008) -http://www.jove.com/details.php?id=960 doi: 10.3791/960.
For all inquiries, please contact Bart Roucourt, Manager Contract Research.