Title:The Effect of Spinal Cord Injury on Beta-Amyloid Plaque Pathology in TgCRND8 Mouse Model of Alzheimer’s Disease
Volume: 17
Issue: 6
Author(s): Qiuju Yuan*, Jian Yang, Yan-Fang Xian, Rong Liu, Chun W. Chan, Wutian Wu and Zhi-Xiu Lin*
Affiliation:
- Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong,China
- Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong,China
Keywords:
Axonal injury, β amyloid, amyloid precursor protein, Alzheimer's disease, amyloid plaques, traumatic spinal cord
injury.
Abstract:
Background: The accumulation and aggregation of Aβ as amyloid plaques, the hallmark
pathology of the Alzheimer's disease, has been found in other neurological disorders, such as traumatic
brain injury. The axonal injury may contribute to the formation of Aβ plaques. Studies to date have
focused on the brain, with no investigations of spinal cord, although brain and cord share the same
cellular components.
Objective: We utilized a spinal cord transection model to examine whether spinal cord injury acutely
induced the onset or promote the progression of Aβ plaque 3 days after injury in TgCRND8 transgenic
model of AD.
Methods: Spinal cord transection was performed in TgCRND8 mice and its littermate control wild type
mice at the age of 3 and 20 months. Immunohistochemical reactions/ELISA assay were used to
determine the extent of axonal damage and occurrence/alteration of Aβ plaques or levels of Aβ at different
ages in the spinal cord of TgCRND8 mice.
Results: After injury, widespread axonal pathology indicated by intra-axonal co-accumulations of APP
and its product, Aβ, was observed in perilesional region of the spinal cord in the TgCRND8 mice at the
age of 3 and 20 months, as compared to age-matched non-TgCRND8 mice. However, no Aβ plaques
were found in the TgCRND8 mice at the age of 3 months. The 20-month-old TgCRND8 mice with established
amyloidosis in spinal cord had a reduction rather than increase in plaque burden at the lesion
site compared to the tissue adjacent to the injured area and corresponding area in sham mice following
spinal cord transection. The lesion site of spinal cord area was occupied by CD68 positive macrophages/
activated microglia in injured mice compared to sham animals. These results indicate that spinal
cord injury does not induce the acute onset and progression of Aβ plaque deposition in the spinal cord of
TgCRND8 mice. Conversely, it induces the regression of Aβ plaque deposition in TgCRND8 mice.
Conclusion: The findings underscore the dependence of traumatic axonal injury in governing acute Aβ
plaque formation and provide evidence that Aβ plaque pathology may not play a role in secondary injury
cascades following spinal cord injury.
