P1‐142: Using DTI for noninvasive evaluation of axonal damage caused by exposure of axon terminals to beta‐amyloid

Background: Amyloid Beta (Ab) is the major toxic mediator responsible for synaptic deficits in the early stage of Alzheimer's disease (AD). Recent studies showed that synaptic Ab can further cause distal axonopathy and neurodegeneration leading to neuronal loss. We explored an in vivo setup to demonstrate the synaptic Ab to cause pre-synaptic axonal degeneration. Methods: Ab1-42 (4 n mole, N = 6) or saline (N = 6) were injected at the right optic tract axonal terminals in 12-week-old C57BL/6 mice. In 1 and 3 months after Ab injection, mice were placed in a Bruker 4.7T small animal MRI for Diffusion Tensor Imaging (DTI) with slice thickness 0.5 mm, field of view of 2cm x 2cm and matrix 128 x 128 (zero filling to 256 x 256) to cover the visual system from eyes to superior colliculus. Animals were then sacrificed. The optic tract and nerve were examined using a primary antibody against phosphorylated neurofilament (pNF, SMI-31) and myelin basic protein (MBP). Results: In optic tract, the Ab-injected side (right side) of the tracts showed a 12-16% decrease of axial diffusivity (P