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The central role of T-cell memory in Alzheimer’s disease vaccination

机译：T细胞记忆在阿尔茨海默氏病疫苗接种中的核心作用

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Alzheimer's disease (AD) is the most common progressive neurodegenerative brain disease as well as the most common dementia among the elderly. In the future as the average lifespan continues to extend, the number of AD patients will continue to grow. Amyloid-beta (Aβ) peptides, in both soluble oligomeric, and insoluble forms, are key in the neuropathogenesis of AD and have thus been a therapeutic target for vaccines. Multiple Aβ vaccination strategies in animal models of AD have demonstrated a marked reduction in both amyloid burden and neurocognitive deficits. Due to the success of these studies, initial human clinical trials of an active Aβ vaccine were conducted. These were discontinued due to the development of meningoencephalitis in approximately 6% of the vaccinated AD patients. Studies examining the brains of Aβ-vaccinated patients developing meningoencephalitis implicate Aβ-reactive T-cell subsets as major components of this deleterious response to active Aβ vaccination. To subvert possible meningoencephalitis resulting from Aβ vaccination second generation of vaccines has been more recently developed. These however have met with little success in humans. To build on these findings, an understanding of the role of T-cells in vaccination against Aβ is presented in this review. Various methods of Aβ immunotherapy are reviewed including studies in both animal models and humans. Recent works suggest that Aβ-derived peptides delivered intranasally or transcutaneously results in effective clearance of Aβ plaques and improvement of cognitive function in animal models of AD. Moreover, undesired T-cell reactivity appeared to be considerably reduced compared with other active immunization strategies. In spite of the past clinical studies, these findings imply that Aβ vaccination may be both efficacious and safe depending route of delivery, adjuvant choice, and Aβ epitope administered.
机译：阿尔茨海默氏病（AD）是老年人中最常见的进行性神经退行性脑部疾病，也是最常见的痴呆症。未来，随着平均寿命的不断延长，AD患者的人数将继续增长。可溶性寡聚和不溶形式的淀粉样蛋白-β（Aβ）肽是AD神经病变的关键，因此已成为疫苗的治疗靶标。 AD动物模型中的多种Aβ疫苗接种策略已证明淀粉样蛋白负荷和神经认知缺陷均明显减少。由于这些研究的成功，进行了活性Aβ疫苗的初步人类临床试验。由于约6％的免疫接种AD患者发生脑膜脑炎而中断了治疗。研究检查接种Aβ疫苗的脑膜脑炎患者大脑的研究表明，Aβ反应性T细胞亚群是这种对主动Aβ疫苗有害反应的主要成分。为了破坏由Aβ疫苗接种引起的可能的脑膜脑炎，最近已经开发了第二代疫苗。然而，这些在人类中几乎没有成功。基于这些发现，本文综述了T细胞在针对Aβ疫苗接种中的作用。对Aβ免疫疗法的各种方法进行了综述，包括在动物模型和人类中的研究。近期的研究表明，鼻内或经皮递送的Aβ衍生肽可有效清除Aβ斑块，并改善AD动物模型的认知功能。此外，与其他主动免疫策略相比，不良T细胞反应性似乎已大大降低。尽管过去进行了临床研究，但这些发现暗示Aβ疫苗接种既有效又安全，具体取决于分娩途径，佐剂选择和Aβ表位的给药。

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