Imaging biophysics of axonal transport with MEMRI: Optic tract transport is altered in mouse model of Alzheimer's disease

Abstract

Recent evidence implicates transport defects in neurodegeneration, epilepsy, and glaucoma. The oriented neuronal projections from the retinal ganglion cells in the optic tract proved an excellent system in which to detect the effects of genetics or disease on axonal transport. Manganese-enhanced MRI (MEMRI) allows tracing of neuronal tracts in the optic tract of living animals, which thus offers the potential to measure the dynamics of axonal transport over time in genetically controlled animals (1, 2). We previously reported in timelapse MRI of intensity changes along the optic tract that Mn^(++) transports more slowly in the optic tract of mice with a genetic knock-out of the kinesin light chain gene (3). Conventional kinesin is the cellular motor thought to mediate a portion of axonal transport. This result demonstrated that MEMR imaging is sensitive enough to detect transport differences between genetically distinct mice. Here we report the effect of genetic manipulation of amyloid precursor protein (APP) on Mn^(++) transport by time-lapse T1-weighted slab images acquired at 6 min intervals over the course of 3.0 hr after injection of Mn^(++) into the posterior chamber of the eye. We tested 16 mo old mice expressing a human APP mutant protein known to cause Alzheimer's disease (SwAPP) and their wildtype littermates (TTA)(4). At this age, this mutant mouse strain has Alzheimer's-type plaques in the brain.

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