Inflammatory plasma profile in genetic symptomatic and presymptomatic Frontotemporal Dementia - A GENFI study.
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Fenoglio Chiara, Serpente Maria, Arcaro Marina, Carandini Tiziana, Sacchi Luca, Pintus Manuela, Rotondo Emanuela, Borracci Vittoria, Ghezzi Laura, Bouzigues Arabella, Russell Lucy L, Foster Phoebe H, Ferry-Bolder Eve, van Swieten John C, Jiskoot Lize C, Seelaar Harro, Sánchez Valle Raquel, Laforce Robert, Graff Caroline, Vandenberghe Rik, de Mendonça Alexandre, Tiraboschi Pietro, Santana Isabel, Gerhard Alexander, Levin Johannes, Sorbi Sandro, Otto Markus, Pasquier Florence, Ducharme Simon, Butler Chris R, Ber Isabelle Le, Finger Elizabeth, Carmela Tartaglia Maria, Masellis Mario, Rowe James B, Synofzik Matthis, Moreno Fermin, Borroni Barbara, Rohrer Jonathan D, Arighi Andrea, Galimberti Daniela, Genetic FTD Initiative GENFI
Аннотация
METHODS: 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)].
RESULTS: 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.
CONCLUSION: 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.