Alzheimer’s disease (AD) is the major form of dementia in the elderly population. The main neuropathological changes in AD patients are neuronal death, synaptic alterations, brain inflammation, and the presence of cerebral protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Compelling evidence suggests that the misfolding, aggregation, and cerebral deposition of amyloid-beta (Aβ) plays a central role in the disease. Thus, prevention and removal of misfolded protein aggregates is considered a promising strategy to treat AD. In the present study, we describe that the development of cerebral amyloid plaques in a transgenic mice model of AD (Tg2576) was significantly reduced by 40–80% through exchanging whole blood with normal blood from wild type mice having the same genetic background. Importantly, such reduction resulted in improvement in spatial memory performance in aged Tg2576 mice. The exact mechanism by which blood exchange reduces amyloid pathology and improves memory is presently unknown, but measurements of Aβ in plasma soon after blood exchange suggest that mobilization of Aβ from the brain to blood may be implicated. Our results suggest that a target for AD therapy may exist in the peripheral circulation, which could open a novel disease-modifying intervention for AD.

阿尔茨海默病（AD）是老年人痴呆症的主要形式。 AD患者的主要神经病理学变化是神经元死亡、突触改变、脑部炎症以及以淀粉样斑块和神经原纤维缠结形式存在的脑蛋白聚集体。令人信服的证据表明，β 淀粉样蛋白 (Aβ) 的错误折叠、聚集和脑沉积在该疾病中发挥着核心作用。因此，预防和去除错误折叠的蛋白质聚集体被认为是治疗 AD 的有前途的策略。在本研究中，我们描述了通过将全血与具有相同遗传背景的野生型小鼠的正常血液交换，AD转基因小鼠模型（Tg2576）中脑淀粉样斑块的形成显着减少了40-80%。重要的是，这种减少导致老年 Tg2576 小鼠空间记忆性能的改善。目前尚不清楚血液交换减少淀粉样蛋白病理并改善记忆的确切机制，但血液交换后不久对血浆中 Aβ 的测量表明，Aβ 从大脑动员到血液可能与此有关。我们的结果表明，AD 治疗的靶点可能存在于外周循环中，这可能为 AD 开辟一种新的疾病缓解干预措施。