Neuroscience Center, Department of Neurology, The First Hospital of Jilin University, Changchun, China.
Department of Neurobiology, Care Sciences & Society, Division of Neurogeriatrcs, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, Sweden.
J Neuroinflammation. 2024 Jan 4;21(1):5. doi: 10.1186/s12974-023-03003-5.
A key pathological factor of Alzheimer's disease (AD), the most prevalent form of age-related dementia in the world, is excessive β-amyloid protein (Aβ) in extracellular aggregation in the brain. And in the peripheral blood, a large amount of Aβ is derived from platelets. So far, the causality between the levels of peripheral blood Aβ and its aggregation in the brain, particularly the role of the peripheral blood Aβ in the pathology of AD, is still unclear. And the relation between the peripheral blood Aβ and tau tangles of brain, another crucial pathologic factor contributing to the pathogenesis of AD, is also ambiguous. More recently, the anti-Aβ monoclonal antibodies are approved for treatment of AD patients through declining the peripheral blood Aβ mechanism of action to enhance plasma and central nervous system (CNS) Aβ clearance, leading to a decrease Aβ burden in brain and improving cognitive function, which clearly indicates that the levels of the peripheral blood Aβ impacted on the Aβ burden in brain and involved in the pathogenesis of AD. In addition, the role of peripheral innate immune cells in AD remains mostly unknown and the results obtained were controversial. In the present review, we summarize recent studies on the roles of peripheral blood Aβ and the peripheral innate immune cells in the pathogenesis of AD. Finally, based on the published data and our own work, we believe that peripheral blood Aβ plays an important role in the development and progression of AD by impacting on the peripheral innate immune cells.
阿尔茨海默病（AD）是世界上最常见的与年龄相关的痴呆症，其一个关键的病理因素是大脑中细胞外聚集的过量β-淀粉样蛋白（Aβ）。而在外周血液中，大量的 Aβ 来源于血小板。迄今为止，外周血 Aβ 水平与其在大脑中的聚集之间的因果关系，特别是外周血 Aβ 在 AD 病理中的作用仍不清楚。外周血 Aβ 与另一个导致 AD 发病机制的关键病理因素——脑内 tau 缠结之间的关系也不明确。最近，抗 Aβ 单克隆抗体通过降低外周血 Aβ 的作用机制来治疗 AD 患者，从而增强血浆和中枢神经系统（CNS）Aβ 的清除，导致脑内 Aβ 负荷减少和认知功能改善，这清楚地表明外周血 Aβ 的水平影响脑内 Aβ 负荷，并参与 AD 的发病机制。此外，外周固有免疫细胞在 AD 中的作用仍知之甚少，且结果存在争议。在本综述中，我们总结了最近关于外周血 Aβ 和外周固有免疫细胞在 AD 发病机制中的作用的研究。最后，基于已发表的数据和我们自己的工作，我们认为外周血 Aβ 通过影响外周固有免疫细胞在 AD 的发展和进展中发挥重要作用。
