Aging Impacts Significantly on Neuronal Transport in Normal Mice but Not in an Accelerated Mouse Model of Amyloid Beta Pathology

Umer Abdur Rahim Khan¹, Anne Bertrand^1,2, 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.