Satoshi Minoshima1, Donna Cross. 1. Departments of Radiology and Bioengineering, University of Washington, 1959 N.E. Pacific Street,Seattle, WA 98195-7115, USA. minoshim@u.washington.edu
Abstract
PURPOSE: MRI using manganese as a trans-synaptic axonal tracing agent can unveil dynamics of axonal transport in living subjects. We use this technology to test the hypotheses if impaired axonal transport is a significant pathophysiological process in aging and early Alzheimer's disease (AD) and in part accounting for "selective vulnerability" of projection neurons in AD. METHODS: To allow quantitative assessment of axonal transport in vivo, we developed voxel-based statistical mapping technology as well as a tracer kinetic modeling method based on mass transport for manganese-enhanced MRI to estimate axonal transport rates in aging rats and AD transgenic mice. RESULTS: These techniques demonstrated manganese-enhanced signal changes in axonal projections of the olfactory tract and decreased axonal transport rates in rodent models of aging and AD. CONCLUSION: Altered axonal transport may be a critical pathophysiological process in aging and AD. Manganese-enhanced MRI provides exciting opportunities for the investigations of altered axonal transport in AD and related disorders.
PURPOSE: MRI using manganese as a trans-synaptic axonal tracing agent can unveil dynamics of axonal transport in living subjects. We use this technology to test the hypotheses if impaired axonal transport is a significant pathophysiological process in aging and early Alzheimer's disease (AD) and in part accounting for "selective vulnerability" of projection neurons in AD. METHODS: To allow quantitative assessment of axonal transport in vivo, we developed voxel-based statistical mapping technology as well as a tracer kinetic modeling method based on mass transport for manganese-enhanced MRI to estimate axonal transport rates in aging rats and ADtransgenic mice. RESULTS: These techniques demonstrated manganese-enhanced signal changes in axonal projections of the olfactory tract and decreased axonal transport rates in rodent models of aging and AD. CONCLUSION: Altered axonal transport may be a critical pathophysiological process in aging and AD. Manganese-enhanced MRI provides exciting opportunities for the investigations of altered axonal transport in AD and related disorders.
Authors: Michael B Steketee; Stavros N Moysidis; Xiao-Lu Jin; Jessica E Weinstein; Wolfgang Pita-Thomas; Hemalatha B Raju; Siraj Iqbal; Jeffrey L Goldberg Journal: Proc Natl Acad Sci U S A Date: 2011-11-07 Impact factor: 11.205
Authors: Donna J Cross; Yoshimi Anzai; Eric C Petrie; Nathalie Martin; Todd L Richards; Kenneth R Maravilla; Elaine R Peskind; Satoshi Minoshima Journal: J Nucl Med Date: 2013-06-26 Impact factor: 10.057
Authors: Gorazd B Stokin; Angels Almenar-Queralt; Shermali Gunawardena; Elizabeth M Rodrigues; Tomás Falzone; Jungsu Kim; Concepción Lillo; Stephanie L Mount; Elizabeth A Roberts; Eileen McGowan; David S Williams; Lawrence S B Goldstein Journal: Hum Mol Genet Date: 2008-08-11 Impact factor: 6.150