Immunization with the SDPM1 peptide lowers amyloid plaque burden and improves cognitive function in the APPswePSEN1(A246E) transgenic mouse model of Alzheimer's disease.
Immunization with the SDPM1 peptide lowers amyloid plaque burden and improves cognitive function in the APPswePSEN1(A246E) transgenic mouse model of Alzheimer's disease.
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DOI：
10.1016/j.nbd.2010.05.013
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发表时间：
2010-09
影响因子：
6.1
通讯作者：
Martin PT
中科院分区：
文献类型：
--
作者：
Wang CM;Devries S;Camboni M;Glass M;Martin PT
疫苗接种已成为治疗阿尔茨海默病（AD）的重要治疗方法，然而，用Aβ淀粉样蛋白免疫可能具有不希望的、潜在致命的副作用。在这里，我们展示了一种替代的肽模拟表位疫苗策略，使用SDPM 1肽。SDPM 1是一种由半胱氨酸结合的20个氨基酸的肽，其结合Aβ1-40-和Aβ1-42-淀粉样蛋白的四聚体形式并阻断随后的Aβ淀粉样蛋白聚集。用SDPM 1免疫小鼠诱导具有与SDPM 1肽相同生物活性的肽模拟表位抗体。当在淀粉样斑块形成开始之前进行时，APPswePSEN 1（A246 E）转基因小鼠的SDPM 1疫苗接种减少了大脑中的淀粉样斑块负荷以及Aβ1-40和Aβ1-42水平，改善了莫里斯水迷宫测试中的认知表现，并且没有导致T细胞对免疫原性或Aβ肽或脑部炎症的反应增加。当斑块负荷已经显著后进行时，SDPM 1免疫仍然显著降低APPswePSEN 1（A246 E）脑中淀粉样斑块负荷和Aβ1-40/1-42肽水平，而不诱导致脑炎性T细胞应答或脑炎症，但在此阶段进行治疗并不能改善认知功能。这些实验证明了阿尔茨海默病的新型疫苗方法的功效，其中使用Aβ1-40/1-42淀粉样蛋白特异性结合和阻断肽进行免疫接种以抑制神经病理学和认知功能障碍的发展。
Vaccination has become an important therapeutic approach to the treatment of Alzheimer’s disease (AD), however, immunization with Aβ amyloid can have unwanted, potentially lethal, side effects. Here we demonstrate an alternative peptide-mimotope vaccine strategy using the SDPM1 peptide. SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of Aβ1–40- and Aβ1–42-amyloid and blocks subsequent Aβ amyloid aggregation. Immunization of mice with SDPM1 induced peptide mimotope antibodies with the same biological activity as the SDPM1 peptide. When done prior to the onset of amyloid plaque formation, SDPM1 vaccination of APPswePSEN1(A246E) transgenic mice reduced amyloid plaque burden and Aβ1–40 and Aβ1–42 levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or Aβ peptides or brain inflammation. When done after plaque burden was already significant, SDPM1 immunization still significantly reduced amyloid plaque burden and Aβ1–40/1–42 peptide levels in APPswePSEN1(A246E) brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function. These experiments demonstrate the efficacy of a novel vaccine approach for Alzheimer’s disease where immunization with an Aβ1–40/1–42 amyloid-specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction.
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影响因子：
16.2
作者：
Hock, C;Konietzko, U;Nitsch, RM
通讯作者：
Nitsch, RM
影响因子：
--
作者：
Lemere, Cynthia A.
通讯作者：
Lemere, Cynthia A.
影响因子：
25
作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH
DOI：
10.1073/pnas.95.11.6448
发表时间：
1998-05-26
影响因子：
11.1
作者：
Lambert, MP;Barlow, AK;Klein, WL
通讯作者：
Klein, WL
影响因子：
5.5
作者：
Kutzler, Michele A.;Cao, Chuanhai;Ugen, Kenneth E.
通讯作者：
Ugen, Kenneth E.