University of Lille, Lille, France; Inserm UMR-S 1172, "Alzheiumer & Tauopathies", Lille, France; Labex DISTALZ, Lille, France.
University of Lille, Lille, France; Inserm UMR-S 1172, "Alzheiumer & Tauopathies", Lille, France; Labex DISTALZ, Lille, France.
Biomed J. 2018 Feb;41(1):21-33. doi: 10.1016/j.bj.2018.01.003. Epub 2018 Mar 20.
Alzheimer's Disease (AD) is a chronic neurodegenerative disorder and the most common type of dementia (60-80% of cases). In 2016, nearly 44 million people were affected by AD or related dementia. AD is characterized by progressive neuronal damages leading to subtle and latter obvious decline in cognitive functions including symptoms such as memory loss or confusion, which ultimately require full-time medical care. Its neuropathology is defined by the extracellular accumulation of amyloid-β (Aβ) peptide into amyloid plaques, and intraneuronal neurofibrillary tangles (NFT) consisting of aggregated hyper- and abnormal phosphorylation of tau protein. The latter, identified also as Tau pathology, is observed in a broad spectrum of neurological diseases commonly referred to as "Tauopathies". Besides these lesions, sustained neuroinflammatory processes occur, involving notably micro- and astro-glial activation, which contribute to disease progression. Recent findings from genome wide association studies further support an instrumental role of neuroinflammation. While the interconnections existing between this innate immune response and the amyloid pathogenesis are widely characterized and described as complex, elaborated and evolving, only few studies focused on Tau pathology. An adaptive immune response takes place conjointly during the disease course, as indicated by the presence of vascular and parenchymal T-cell in AD patients' brain. The underlying mechanisms of this infiltration and its consequences with regards to Tau pathology remain understudied so far. In the present review, we highlight the interplays existing between Tau pathology and the innate/adaptive immune responses.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，也是最常见的痴呆症类型（占 60-80%）。2016 年，全球约有 4400 万人患有 AD 或相关痴呆症。AD 的特征是进行性神经元损伤，导致认知功能逐渐下降，最终出现记忆力减退或意识混乱等明显症状，需要全职医疗护理。其神经病理学定义为细胞外淀粉样β（Aβ）肽的积累形成淀粉样斑块，以及由 tau 蛋白过度和异常磷酸化聚集形成的神经元内神经原纤维缠结（NFT）。后者也被称为 Tau 病理学，存在于广泛的被称为“Tau 病”的神经退行性疾病中。除了这些病变，还会发生持续的神经炎症过程，包括小胶质细胞和星形胶质细胞的激活，这有助于疾病的进展。全基因组关联研究的最新发现进一步支持了神经炎症的重要作用。虽然先天免疫反应与淀粉样发病机制之间的相互联系已经被广泛研究和描述为复杂、详细和不断发展的，但只有少数研究集中在 Tau 病理学上。在疾病过程中，会发生适应性免疫反应，如 AD 患者大脑中血管和实质 T 细胞的存在所表明的那样。到目前为止，这种浸润的潜在机制及其对 Tau 病理学的后果仍研究不足。在本综述中，我们强调了 Tau 病理学与先天/适应性免疫反应之间的相互作用。
