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Journal of Alzheimer's disease : JAD · 2024

Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia: A GENFI Study.

СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Serpente Maria, Fenoglio Chiara, 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, Le Ber Isabelle, Finger Elizabeth, Tartaglia Maria Carmela, Masellis Mario, Rowe James B, Synofzik Matthis, Moreno Fermin, Borroni Barbara, Rohrer Jonathan D, Arighi Andrea, Galimberti Daniela, Genetic FTD Initiative GENFI

Аннотация

BACKGROUND: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and Progranulin (GRN) genes are not well understood.

OBJECTIVE: This study aimed to profile the expression levels of lncRNAs in peripheral blood mononuclear cells collected within the GENetic Frontotemporal dementia Initiative (GENFI).

METHODS: Fifty-three lncRNAs were analyzed with the OpenArray Custom panel, in 131 patients with mutations in C9ORF72, MAPT, and GRN, including 68 symptomatic mutation carriers (SMC) and 63 presymptomatic mutation carriers (PMC), compared with 40 non-carrier controls (NC).

RESULTS: Thirty-eight lncRNAs were detectable; the relative expression of NEAT1 and NORAD was significantly higher in C9ORF72 SMC as compared with NC. GAS5 expression was instead significantly lower in the GRN group versus NC. MAPT carriers showed no significant deregulations. No significant differences were observed in PMC. Disease duration did not correlate with lncRNA expression.

CONCLUSIONS: NEAT1 and NORAD are upregulated in C9ORF72 SMC and GAS5 levels are downregulated in GRN SMC, underlining lncRNAs' relevance in FTD and their potential for biomarker development. Further validation and mechanistic studies are crucial for clinical implications.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты