In vivo imaging of axonal transport using MRI: aging and Alzheimer's disease.

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.