Background: The accumulation and aggregation of Aβ as amyloid plaques, the hallmark pathology of the Alzheimers 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.

背景：Aβ 作为淀粉样斑块的积累和聚集是阿尔茨海默病的标志性病理，已在其他神经系统疾病中发现，例如外伤性脑损伤。轴突损伤可能有助于 Aβ 斑块的形成。迄今为止的研究都集中在大脑上，没有研究脊髓，尽管大脑和脊髓具有相同的细胞成分。

目的：我们利用脊髓横断模型来检查脊髓损伤是否在 TgCRND8 转基因 AD 模型中在损伤后 3 天急性诱导 Aβ 斑块的发作或促进 Aβ 斑块的进展。

方法：在 3 个月和 20 个月大的 TgCRND8 小鼠及其同窝对照野生型小鼠中进行脊髓横断。免疫组织化学反应/ELISA 测定用于确定 TgCRND8 小鼠脊髓中不同年龄的轴突损伤程度和 Aβ 斑块的发生/改变或 Aβ 水平。

结果：受伤后，与年龄相比，在 3 个月和 20 个月大的 TgCRND8 小鼠脊髓的病灶周围区域观察到广泛的轴突病理，由 APP 及其产物 Aβ 的轴突内共积累所指示。 -匹配的非 TgCRND8 小鼠。然而，在 3 个月大的 TgCRND8 小鼠中没有发现 Aβ 斑块。20 个月大的 TgCRND8 小鼠，在脊髓横断后，与损伤区域附近的组织和假小鼠的相应区域相比，在损伤部位的斑块负荷减少而不是增加。与假手术动物相比，受伤小鼠的脊髓区域的病变部位被 CD68 阳性巨噬细胞/活化的小胶质细胞占据。这些结果表明脊髓损伤不会诱导 TgCRND8 小鼠脊髓中 Aβ 斑块沉积的急性发作和进展。相反，它诱导 TgCRND8 小鼠中 Aβ 斑块沉积的消退。

结论：研究结果强调了创伤性轴突损伤在控制急性 Aβ 斑块形成​​方面的依赖性，并提供证据表明 Aβ 斑块病理可能不会在脊髓损伤后的继发性损伤级联反应中发挥作用。