Amyloid pathology in spinal cord of the transgenic Alzheimer's disease mice is correlated to the corticospinal tract pathway

Abstract

The transgenic TgCRND8 mouse is widely used as an animal model of Alzheimer's disease (AD) and exhibits an early onset of senile plaque pathogenesis in the brain. Here we report that TgCRND8 mice also have amyloid-beta (Abeta) neuropathology in spinal cord. TgCRND8 mice began to show obvious Abeta deposition in both gray matter of dorsal horn and white matter in the central part of dorsal column of the spinal cord at 10 months of age onward. Further experiments showed that the distribution of Abeta deposition in the spinal cord corresponds to the corticospinal tract pathway and its projection regions in TgCRND8 mice. We hypothesized that neurons in the sensorimotor cortex is the source of the Abeta peptide deposited in the spinal cord of these mice. To test the hypothesis, we ablated the sensorimotor cortex to interrupt connections between the sensorimotor cortex and spinal cord. We found that Abeta burden was significantly reduced in the denervated side compared to the contralateral side. Our results suggest that the sensorimotor cortex might be the primary source of Abeta in spinal cord of TgCRND8 mice. This is consistent with the observation that the sensorimotor cortex is one region particularly vulnerable during the progression of AD. The characteristics of Abeta distribution in TgCRND8 mice suggest that there are other ways related to the formation of Abeta plaques in addition to the terminal and synaptic release of Abeta.