Axonal Terminals Exposed to Amyloid-β May Not Lead to Pre-Synaptic Axonal Damage

Synaptic deficits and neuronal loss are the major pathological manifestations of Alzheimer's disease. However, the link between the early synaptic loss and subsequent neurodegeneration is not entirely clear. Cell culture studies have shown that amyloid-β (Aβ) applied to axonal terminals can cause retrograde degeneration leading to the neuronal loss, but this process has not been demonstrated in live animals.

To test if Aβ applied to retinal ganglion cell axonal terminals can induce axonal damage in the optic nerve and optic tract in mice.

Aβ was injected into the terminal field of the optic tract, in the left lateral geniculate nucleus of wildtype C57BL/6 mice. Following the injection, monthly diffusion tensor imaging was performed. Three months after the injection, mice underwent visual evoked potential recordings, and then sacrificed for immunohistochemical examination.

There were no significant changes seen with diffusion tensor imaging in the optic nerve and optic tract 3 months after the Aβ injection. The myelin and axons in these regions remained intact according to immunohistochemistry. The only significant changes observed in this study were delayed transduction and reduced amplitude of visual evoked potentials, although both Aβ and its reversed form caused similar changes.

Despite the published in vitro studies, there was no significant axonal damage in the optic nerve and optic tract after injecting Aβ onto retinal ganglion cell axonal terminals of wildtype C57BL/6 mice.