炎症被认为是神经退行性疾病（包括额颞叶痴呆（FTD））的关键因素。一些关于散发性 FTD 的研究导致了不确定的结果，而缺乏关于遗传性 FTD 的大规模研究。本研究的目的是确定在基因额颞叶痴呆计划 (GENFI) 内收集的大量遗传性 FTD 中的细胞因子和趋化因子血浆循环水平。使用 Mesoscale 技术分析了 434 个血浆样本中 30 种炎症因子的水平，包括94 有症状突变携带者[(SMC)； 15 例在微管相关蛋白 Tau (MAPT) 中发生突变，34 例在颗粒体蛋白前体 (GRN) 中发生突变，45 例在第 9 号染色体开放阅读框 (C9ORF)72] 中发生突变，168 例出现症状前突变携带者（PMC；34 MAPT、70 GRN 和 64 C9ORF72），173 例非突变携带者-载体对照(NC)]。与NC相比，MAPT和GRN SMC中以下细胞因子显着上调(P<0.05)：肿瘤坏死因子(TNF)α、白细胞介素(IL)-7、IL-15、IL-16、 IL-17A。此外，仅在 GRN SMC 中，其他因子上调，包括：IL-1β、IL-6、IL-10、IL-12/IL-23p40、eotaxin、eotaxin-3、干扰素 γ 诱导蛋白 (IP-10) ，单核细胞趋化蛋白（MCP）4。相反，与 NC 相比，SMC 中的 IL-1α 水平降低。 PMC 中这种细胞因子的水平也显着降低，与突变类型无关。在 SMC 中，未发现疾病持续时间与细胞因子和趋化因子水平之间存在相关性。考虑到 NfL 和 GFAP 水平，正如预期的那样，与 NC 相比，SMC 中观察到显着增加。即使根据突变基因对有症状的患者进行分层，这些平均值的差异仍然显着（P<0.0001）。相反，考虑 NfL、GFAP 和改变的炎症分子的水平，没有出现显着的相关性。我们发现 MAPT 和 GRN SMC 中炎症蛋白上调，仅 GRN 中一些特定因素发生改变，而 C9ORF72 携带者中没有看到变化。值得注意的是，SMC 和 PMC 中只有 IL-1α 水平下降，与因果突变的类型无关，表明常见的修饰发生在疾病的临床前阶段。版权所有 © 2024。由 Elsevier Inc. 出版。

Inflammation has been proposed as a crucial player in neurodegeneration, including Frontotemporal Dementia (FTD). A few studies on sporadic FTD lead to inconclusive results, whereas large studies on genetic FTD are lacking. The aim of this study is to determine cytokine and chemokine plasma circulating levels in a large cohort of genetic FTD, collected within the GENetic Frontotemporal dementia Initiative (GENFI).Mesoscale technology was used to analyse levels of 30 inflammatory factors in 434 plasma samples, including 94 Symptomatic Mutation carriers [(SMC); 15 with mutations in Microtubule Associated Protein Tau (MAPT) 34 in Progranulin (GRN) and 45 in Chromosome 9 Open Reading Frame (C9ORF)72], 168 Presymptomatic Mutation Carriers (PMC; 34 MAPT, 70 GRN and 64 C9ORF72) and 173 Non-carrier Controls (NC)].The following cytokines were significantly upregulated (P<0.05) in MAPT and GRN SMC versus NC: Tumor Necrosis Factor (TNF)α, Interleukin (IL)-7, IL-15, IL-16, IL-17A. Moreover, only in GRN SMC, additional factors were upregulated, including: IL-1β, IL-6, IL-10, IL-12/IL-23p40, eotaxin, eotaxin-3, Interferon γ-induced Protein (IP-10), Monocyte Chemotactic Protein (MCP)4. On the contrary, IL-1α levels were decreased in SMC compared with NC. Significantly decreased levels of this cytokine were also found in PMC, independent of the type of mutation. In SMC, no correlations between disease duration and cytokine and chemokine levels were found. Considering NfL and GFAP levels, as expected, significant increases were observed in SMC as compared to NC. These differences in mean values remain significant even when stratifying symptomatic patients by the mutated gene (P<0.0001). Considering instead the levels of NfL, GFAP, and the altered inflammatory molecules, no significant correlations emerged.We showed that inflammatory proteins are upregulated in MAPT and GRN SMC, with some specific factors altered in GRN only, whereas no changes were seen in C9ORF72 carriers. Notably, only IL-1α levels were decreased in both SMC and PMC, independent of the type of causal mutation, suggesting common modifications occurring in the preclinical phase of the disease.Copyright © 2024. Published by Elsevier Inc.