In vivo diffusion tensor imaging of amyloid-β-induced white matter damage in mice.

Background: Diffusion tensor imaging (DTI) suggests the presence of white matter abnormality at the prodromal stage in human Alzheimer's disease (AD). Objective: To use a mouse model of AD to determine whether the white matter abnormality detected by in vivo DTI is associated with functional deficits and axon damage. Methods: Amyloid-beta(1-42) (A beta(1-42)) was injected into the left lateral ventricle in mice. Two months after the injection, in vivo DTI and visual evoked potential (VEP) recordings were performed, followed by immunohistochemistry of phosphorylated neurofilament and myelin basic protein. Results: DTI of A beta(1-42)-treated mice showed a significant increase of radial diffusivity in white matter including the optic nerves and tracts. The abnormality was associated with decreased amplitude and increased latency of VEP. Immunohistochemistry confirmed a significant loss of axons and myelin integrity. Conclusion: White matter damage induced by A beta(1-42) in mice can be detected non-invasively by DTI.