Umer Abdur Rahim Khan1, Anne Bertrand1,2, Hoang Minh Dung1, Dmitry Novikov1, Lindsay Kathleen Hill1, Benjamin Winthrope Little1, Hameetha B. Rajamohamed Sait3, Mesha Shamsie1, Einar M. Sigurdsson3, Youssef Zaim Wadghiri1
Amyloid Beta (A Beta) and tau play an essential role in the Alzheimers disease (AD) pathophysiology. There is in vitro evidence that A Beta oligomers can impair fast axonal transport. Crucially lacking are in vivo non invasive techniques to evaluate neuronal function. Track-Tracing Manganese Enhanced MRI (TT-MEMRI) is currently the only non invasive 4-D volumetric imaging technique to demonstrate neuronal transport perturbations. Applying MEMRI in a transgenic model (Tg2576) of A Beta pathology by expressing human APP mutation confirmed the deleterious effect of A Beta on neuronal transport measured by a decrease in the rate of signal change. We previously investigated a tau model (JNPL3) using a 7 day time-course period where we showed a significant decrease in neuronal transport function in Tg mice. In the present study, we sought to examine with the same approach an accelerated A Beta mouse model (Tg6799 5xFAD) expressing both APP and PS1 human mutations. Surprisingly, our results show significant decrease in neuronal conduction in the (C57/B6xSJL) WT mice with age contrasting with maintained transport function in Tg 5xFAD with age.