The Neurobiology of Aging

no. 1 DISEASE-MODIFYING EFFECTS OF RESVERATROL IN THE 3XTG-AD MOUSE MODEL OF ALZHEIMER’S DISEASE A. DAL-PAN , C. JULIEN , C. PIERRISNARD , C. TREMBLAY , F. CALON Axes Neurosciences, Centre de recherche du centre hospitalier de l’Université Laval (CHUQ), Québec, QC, Canada . Background: There is a general agreement that disease-modifying treatments will be required for Alzheimer's disease (AD). In this study, we tested the therapeutic potential of two potential disease modifying drugs, namely the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) and resveratrol (RVT), a polyphenolic compound derived from grapes, in the 3xTg-AD mouse model of AD. Methods: Four groups of 3xTg-AD mice received from the age of 12 months a DHA (~0.8 g.kg-1.day-1) or a RVT (~1 g.kg-1.day-1) supplementation for a period of either 6 months or 3 months followed by 3 months of a washout period, to test disease modification. All animals were fed a westernized diet until sacrifice at 18 months of age. Results: Both RVT and DHA improved the exploratory behavior of 3xTg-AD mice. RVT induced decreases of soluble Aβ42/Aβ40 ratio (-42%) and insoluble tau (-93%) in the parieto-temporal cortex of 3xTg-AD mice. Both effects remained significant after a 3-month washout. DHA treatment also led to a decrease of insoluble tau (-74%), an effect lost after the washout period. Finally, both DHA and RVT protected from the increase of soluble drebrin observed in 3xTg-AD mice fed the control diet. Conclusions: These data confirm previous report on a beneficial impact of DHA and RVT in AD models and provide new evidence of disease-modifying effects of RVT on Aβ, tau and synaptic markers, remaining significant 3 months after the end of treatment. Contact information: Axe Neurosciences, Centre de recherche du CHUL (CHUQ), 2705, boul. Laurier, Ste-Foy, QC, Canada, G1V 4G2 [email protected]