WNT signaling: biomarker and target evaluation in Alzheimer's disease

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The invariant failure of Biopharmaceutical pipelines to modify Alzheimer'sdisease (AD) progression indicates the need for new creative solutions beyondcurrently active areas of genetics, amyloid-ß, and Tau pathology. Very recent workfrom our groups and others indicate that novel elements of the canonical and noncanonical WNT signaling pathways could be targeted to modify and monitor ADprogression.In this project we will use multidisciplinary approaches, including brain oriented drug screening, a novel proprietary mouse model of AD, new genetic and pharmacological tools for modulation of WNT/GSK3 and WNT/JNK pathways, humanblood samples from our and the IMI/EMIF platform to identify novel biomarkers of AD progression and a pilot study on metabolomics, to explore the impact on AD ofnovel WNT elements including but not limited to clusterin, DKK1 and Nrf2.Our results in this pathfinder phase with the identification of new candidate targets and drugs for clinical studies will pave the way to therapeutic innovations inthe long-term programme. Indeed, several Biopharma companies have initiated drug development programs aimed at targeting certain components of the WNT signaling pathway, including ligands and other small molecule regulators of Axin1 and GSK-3, and Nrf2 that will be interested in our findings.