Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization
Cessation of Neoangiogenesis in Alzheimer's Disease Follows Amyloid-beta Immunization
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DOI：
10.1038/srep01354
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发表时间：
2013-02-28
影响因子：
4.6
通讯作者：
Jefferies, Wilfred A.
中科院分区：
文献类型：
--
作者：
Biron, Kaan E.;Dickstein, Dara L.;Jefferies, Wilfred A.
阿尔茨海默病（AD）中的致病性新血管生成是由于淀粉样蛋白β（A β）导致的，并导致AD中的血脑屏障（BBB）渗漏。它可能作为对脑血流受损的代偿反应而发生，并在脑血管和AD之间提供了强有力的联系。A β免疫疗法是一种实验性的AD治疗方法;然而，在早期人类临床试验中观察到的意想不到的负面血管副作用表明，我们对A β和AD发病机制的了解是不完整的。我们证明，免疫A β肽中和淀粉样蛋白触发导致新血管生成和逆转在Tg 2576 AD小鼠血管过多。这一过程解决了斑块负荷，表明新血管生成是斑块形成的关键机制。一项荟萃分析表明，在接种疫苗的阿尔茨海默氏症患者中，这似乎是任何治疗干预后血管逆转的第一个例子，并支持调节新血管生成可以修复AD脑损伤的结论。
Pathogenic neoangiogenesis in Alzheimer's disease (AD) is due to amyloid-beta (A beta) and results in blood-brain barrier (BBB) leakiness in AD. It likely occurs as a compensatory response to impaired cerebral blood flow and provides a strong link between brain vascularity and AD. A beta immunotherapy is an experimental treatment for AD; however, unexpected negative vascular side effects seen in early human clinical trials demonstrate that our knowledge of A beta and AD pathogenesis is incomplete. We demonstrate that immunization with A beta peptides neutralizes the amyloid trigger leading to neoangiogenesis and reverses hypervascularity in Tg2576 AD mice. This process resolves plaque burden suggesting that neoangiogenesis is a key mechanism underlying plaque formation. A meta-analysis demonstrated that hypervascular reversion in vaccinated Alzheimer's patients. This appears to be the first example of vascular reversion following any therapeutic intervention and supports the conclusion that modulation of neoangiogenesis may repair damage in the AD brain.