Alberici Antonella, Cristillo Viviana, Gazzina Stefano, Benussi Alberto, Padovani Alessandro, Borroni Barbara
Neurology Clinic, Spedali Civili Hospital, Brescia, Italy.
Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Curr Alzheimer Res. 2018;15(7):602-609. doi: 10.2174/1567205015666180119104825.
Frontotemporal Dementia (FTD) is a neurodegenerative disorder which asymmetrically affects the frontotemporal lobe, characterized by behavioural abnormalities, language impairment, and deficits of executive functions. Genetic studies identified mutations causing the disease, namely Microtubule Associated Protein Tau (MAPT), Granulin (GRN) and chromosome 9 open reading frame 72 (C9orf72) mutations, which contributed to elucidate the molecular pathways involved in brain depositions of either Tau or TAR DNA-binding protein 43 (TDP43) inclusions. However, in the majority of sporadic FTD patients, the mechanisms triggering Tau or TDP43 protein deposition are still to be uncovered.
We aimed to present an extensive evaluation of literature data on immune homeostasis in FTD, in order to provide potentially evidence-based approaches for a disease still orphan of any treatment.
A structured search of bibliographic databases from peer-reviewed literature was pursued focusing on autoimmunity in the brain and FTD.
One-hundred-fourteen papers were included in this review. The majority of studies (32) were represented by extensive literature revision on immunity, central nervous system (CNS) and autoimmunity; neuroimaging papers (11) in autoimmune diseases were evaluated, and immunomodulatory approaches (25) were revised. Six papers were found specifically related to FTD and autoimmune hypothesis, the other papers referring to current state of art on FTD.
Overall this review contribute to expand the knowledge of a possible immune hypothesis in FTD, suggesting therapeutic perspectives in autoimmune related neurodegeneration, to reduce or revert the disease.
额颞叶痴呆（FTD）是一种神经退行性疾病，不对称地影响额颞叶，其特征为行为异常、语言障碍和执行功能缺陷。基因研究确定了导致该疾病的突变，即微管相关蛋白Tau（MAPT）、颗粒蛋白（GRN）和9号染色体开放阅读框72（C9orf72）突变，这些突变有助于阐明Tau或TAR DNA结合蛋白43（TDP43）包涵体在脑内沉积所涉及的分子途径。然而，在大多数散发性FTD患者中，触发Tau或TDP43蛋白沉积的机制仍有待揭示。
我们旨在对FTD免疫稳态的文献数据进行广泛评估，以便为这种仍无任何治疗方法的疾病提供潜在的循证方法。
对来自同行评审文献的书目数据库进行结构化搜索，重点关注脑内自身免疫和FTD。
本综述纳入了114篇论文。大多数研究（32篇）以关于免疫、中枢神经系统（CNS）和自身免疫的广泛文献综述为代表；评估了自身免疫性疾病中的神经影像学论文（11篇），并对免疫调节方法（25篇）进行了综述。发现6篇论文与FTD和自身免疫假说特别相关，其他论文涉及FTD的当前研究现状。
总体而言，本综述有助于扩展对FTD中可能的免疫假说的认识，提出自身免疫相关神经退行性疾病的治疗前景，以减轻或逆转该疾病。
