中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (10): 2305-2310.doi: 10.4103/1673-5374.337054

• 原著:退行性病与再生 • 上一篇    下一篇

DNA疫苗靶向淀粉样蛋白β寡聚体可改善老年APP/PS1/tau三转基因阿尔茨海默病小鼠的认知缺陷

  

  • 出版日期:2022-10-15 发布日期:2022-03-16
  • 基金资助:
    中国国家自然科学基金项目(81870819);辽宁省自然科学基金项目(2019-MS-200)

DNA vaccines targeting amyloid-β oligomer ameliorate cognitive deficits of aged APP/PS1/tau triple-transgenic mouse models of Alzheimer’s disease

Sha Sha1, Xiao-Na Xing2, Tao Wang3, Ying Li1, Rong-Wei Zhang1, Xue-Li Shen1, Yun-Peng Cao4, Le Qu5   

  1. 1Department of Geriatrics, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China; 2Department of Neurology, Shenzhen Luohu People’s Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China; 3College of Life and Health Sciences, Northeastern University, Shenyang, Liaoning Province, China; 4Department of Neurology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China; 5Department of Dermatology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2022-10-15 Published:2022-03-16
  • Contact: Le Qu, PhD, cmuqule@163.com.
  • Supported by:
    This study was supported by the National Nature Science Foundation of China, No. 81870819 (to YPC); and the Natural Science Foundation of Liaoning Province of China, No. 2019-MS-200 (to XNX).

摘要:

淀粉样蛋白β寡聚体而非淀粉样蛋白β单体被认为是阿尔茨海默病的主要引发因子,既往研究显示,假设针对淀粉样蛋白β寡聚体的重组Aβ3-10基因疫苗p(Aβ3-10)10-MT疫苗具有治疗阿尔茨海默病的潜力。为此,实验以左后肢肌肉电穿孔以p(Aβ3-10)10-MT疫苗免疫APP/PS1/tau三转基因阿尔茨海默病小鼠,结果显示该疫苗可更有效地减少大脑皮质和海马中淀粉样蛋白β寡聚体水平和斑块沉积,降低不同类型tau蛋白的水平,减少突触蛋白丢失,并保护突触功能,同时减少神经元的缺失,减轻小鼠的空间记忆障碍,且不会引发脑出血。因而这种新型的DNA疫苗可安全有效治疗阿尔茨海默病的潜力。

https://orcid.org/0000-0002-6923-5364 (Le Qu)

关键词: 免疫治疗, 淀粉样蛋白β寡聚体, tau过度磷酸化, 突触功能, 神经元缺失, 认知障碍, 斑块沉积, DNA疫苗

Abstract: The amyloid-β (Aβ) oligomer, rather than the Aβ monomer, is considered to be the primary initiator of Alzheimer’s disease. It was hypothesized that p(Aβ3–10)10-MT, the recombinant Aβ3–10 gene vaccine of the Aβ oligomer has the potential to treat Alzheimer’s disease. In this study, we intramuscularly injected the p(Aβ3–10)10-MT vaccine into the left hindlimb of APP/PS1/tau triple-transgenic mice, which are a model for Alzheimer’s disease. Our results showed that the p(Aβ3–10)10-MT vaccine effectively reduced Aβ oligomer levels and plaque deposition in the cerebral cortex and hippocampus, decreased the levels tau protein variants, reduced synaptic loss, protected synaptic function, reduced neuron loss, and ameliorated memory impairment without causing any cerebral hemorrhaging. Therefore, this novel DNA vaccine, which is safe and highly effective in mouse models of Alzheimer’s disease, holds a lot of promise for the treatment of Alzheimer’s disease in humans.

Key words: Aβ oligomers, cognitive dysfunction, DNA vaccine, immunotherapy, neuron loss, plaque deposits, synaptic function, tau hyperphosphorylation