Department of Geriatrics, the Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, 266071, Shandong Province, China.
Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, No.308 Ningxia Road, Qingdao, 266071, China.
Neuromolecular Med. 2020 Dec;22(4):464-473. doi: 10.1007/s12017-020-08612-4. Epub 2020 Sep 7.
Alzheimer's disease (AD) is commonly considered as the most prominent dementing disorder globally and is characterized by the deposition of misfolded amyloid-β (Aβ) peptide and the aggregation of neurofibrillary tangles. Immunological disturbances and neuroinflammation, which result from abnormal immunological reactivations, are believed to be the primary stimulating factors triggering AD-like neuropathy. It has been suggested by multiple previous studies that a bunch of AD key influencing factors might be attributed to genes encoding human leukocyte antigen (HLA), whose variety is an essential part of human adaptive immunity. A wide range of activities involved in immune responses may be determined by HLA genes, including inflammation mediated by the immune response, T-cell transendothelial migration, infection, brain development and plasticity in AD pathogenesis, and so on. The goal of this article is to review the recent epidemiological findings of HLA (mainly HLA class I and II) associated with AD and investigate to what extent the genetic variations of HLA were clinically significant as pathogenic factors for AD. Depending on the degree of contribution of HLA in AD pathogenesis, targeted research towards HLA may propel AD therapeutic strategies into a new era of development.
阿尔茨海默病（AD）通常被认为是全球最突出的痴呆症，其特征是错误折叠的淀粉样蛋白-β（Aβ）肽的沉积和神经原纤维缠结的聚集。免疫失调和神经炎症被认为是触发 AD 样神经病变的主要刺激因素，这是由于异常的免疫反应引起的。多项先前的研究表明，AD 的一些关键影响因素可能归因于编码人类白细胞抗原（HLA）的基因，其多样性是人类适应性免疫的重要组成部分。HLA 基因可能决定了涉及免疫反应的广泛活动，包括免疫反应介导的炎症、T 细胞穿越内皮迁移、感染、大脑发育和 AD 发病机制中的可塑性等。本文的目的是综述 HLA（主要是 HLA Ⅰ类和Ⅱ类）与 AD 相关的最新流行病学发现，并探讨 HLA 遗传变异在多大程度上作为 AD 的致病因素具有临床意义。根据 HLA 在 AD 发病机制中的贡献程度，针对 HLA 的靶向研究可能将 AD 治疗策略推向一个新的发展时代。
