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

Maria Serpente; Chiara Fenoglio; Genetic Frontotemporal Initiative (GENFI); Marina Arcaro; Tiziana Carandini; Luca Sacchi; Manuela Pintus; Emanuela Rotondo; Vittoria Borracci; Laura Ghezzi; Arabella Bouzigues; Lucy L. Russell; Phoebe H. Foster; Eve Ferry-Bolder; John C. Van Swieten; Lize C. Jiskoot; Harro Seelaar; Raquel Sánchez Valle; Robert Laforce; Caroline Graff; Rik Vandenberghe; Alexandre De Mendonça; Pietro Tiraboschi; Isabel Santana; Alexander Gerhard; Johannes Levin; Sandro Sorbi; Markus Otto; Florence Pasquier; Simon Ducharme; Chris R. Butler; Isabelle Le Ber; Elizabeth Finger; Maria Carmela Tartaglia; Mario Masellis; James B. Rowe; Matthis Synofzik; Fermin Moreno; Barbara Borroni; Jonathan D. Rohrer; Andrea Arighi; Daniela Galimberti; Antonella Alberici; Sónia Afonso; Patricia Alves; Sarah Anderl-Straub; Julie De Houwer; Lucia Giannini; Janne M. Papma; Jackie Poos; Rick Van Minkelen

doi:10.3233/JAD-240557

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

Maria Serpente, Chiara Fenoglio, Genetic Frontotemporal Initiative (GENFI), Marina Arcaro, Tiziana Carandini, Luca Sacchi, Manuela Pintus, Emanuela Rotondo, Vittoria Borracci, Laura Ghezzi, Arabella Bouzigues, Lucy L. Russell, Phoebe H. Foster, Eve Ferry-Bolder, John C. Van Swieten, Lize C. Jiskoot, Harro Seelaar, Raquel Sánchez Valle, Robert Laforce, Caroline GraffRik Vandenberghe, Alexandre De Mendonça, Pietro Tiraboschi, Isabel Santana, Alexander Gerhard, Johannes Levin, Sandro Sorbi, Markus Otto, Florence Pasquier, Simon Ducharme, Chris R. Butler, Isabelle Le Ber, Elizabeth Finger, Maria Carmela Tartaglia, Mario Masellis, James B. Rowe, Matthis Synofzik, Fermin Moreno, Barbara Borroni, Jonathan D. Rohrer, Andrea Arighi, Daniela Galimberti^*, Antonella Alberici, Sónia Afonso, Patricia Alves, Sarah Anderl-Straub, Julie De Houwer, Lucia Giannini, Janne M. Papma, Jackie Poos, Rick Van Minkelen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	S187-S196
Journal	Journal of Alzheimer's Disease
Volume	100
Issue number	s1
DOIs	https://doi.org/10.3233/JAD-240557
Publication status	Published - 20 Aug 2024

Bibliographical note

Publisher Copyright:
© 2024 - The authors. Published by IOS Press.

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Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal DementiaFinal published version, 388 KBLicence: CC BY

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Serpente, M., Fenoglio, C., Genetic Frontotemporal Initiative (GENFI), Arcaro, M., Carandini, T., Sacchi, L., Pintus, M., Rotondo, E., Borracci, V., Ghezzi, L., Bouzigues, A., Russell, L. L., Foster, P. H., Ferry-Bolder, E., Van Swieten, J. C., Jiskoot, L. C., Seelaar, H., Sánchez Valle, R., Laforce, R., ... Van Minkelen, R. (2024). Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia: A GENFI Study. Journal of Alzheimer's Disease, 100(s1), S187-S196. https://doi.org/10.3233/JAD-240557

@article{ecbc4de2bfda43e8b00f6b3e0514973a,

title = "Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia: A GENFI Study",

abstract = "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.",

author = "Maria Serpente and Chiara Fenoglio and {Genetic Frontotemporal Initiative (GENFI)} and Marina Arcaro and Tiziana Carandini and Luca Sacchi and Manuela Pintus and Emanuela Rotondo and Vittoria Borracci and Laura Ghezzi and Arabella Bouzigues and Russell, {Lucy L.} and Foster, {Phoebe H.} and Eve Ferry-Bolder and {Van Swieten}, {John C.} and Jiskoot, {Lize C.} and Harro Seelaar and {S{\'a}nchez Valle}, Raquel and Robert Laforce and Caroline Graff and Rik Vandenberghe and {De Mendon{\c c}a}, Alexandre and Pietro Tiraboschi and Isabel Santana and Alexander Gerhard and Johannes Levin and Sandro Sorbi and Markus Otto and Florence Pasquier and Simon Ducharme and Butler, {Chris R.} and {Le Ber}, Isabelle and Elizabeth Finger and Tartaglia, {Maria Carmela} and Mario Masellis and Rowe, {James B.} and Matthis Synofzik and Fermin Moreno and Barbara Borroni and Rohrer, {Jonathan D.} and Andrea Arighi and Daniela Galimberti and Antonella Alberici and S{\'o}nia Afonso and Patricia Alves and Sarah Anderl-Straub and {De Houwer}, Julie and Lucia Giannini and Papma, {Janne M.} and Jackie Poos and {Van Minkelen}, Rick",

note = "Publisher Copyright: {\textcopyright} 2024 - The authors. Published by IOS Press.",

year = "2024",

month = aug,

day = "20",

doi = "10.3233/JAD-240557",

language = "English",

volume = "100",

pages = "S187--S196",

journal = "Journal of Alzheimer's Disease",

issn = "1387-2877",

publisher = "IOS Press BV",

number = "s1",

}

Serpente, M, Fenoglio, C, Genetic Frontotemporal Initiative (GENFI), Arcaro, M, Carandini, T, Sacchi, L, Pintus, M, Rotondo, E, Borracci, V, Ghezzi, L, Bouzigues, A, Russell, LL, Foster, PH, Ferry-Bolder, E, Van Swieten, JC , Jiskoot, LC , Seelaar, H, Sánchez Valle, R, Laforce, R, Graff, C, Vandenberghe, R, De Mendonça, A, Tiraboschi, P, Santana, I, Gerhard, A, Levin, J, Sorbi, S, Otto, M, Pasquier, F, Ducharme, S, Butler, CR, Le Ber, I, Finger, E, Tartaglia, MC, Masellis, M, Rowe, JB, Synofzik, M, Moreno, F, Borroni, B, Rohrer, JD, Arighi, A, Galimberti, D, Alberici, A, Afonso, S, Alves, P, Anderl-Straub, S, De Houwer, J, Giannini, L, Papma, JM , Poos, J & Van Minkelen, R 2024, 'Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia: A GENFI Study', Journal of Alzheimer's Disease, vol. 100, no. s1, pp. S187-S196. https://doi.org/10.3233/JAD-240557

TY - JOUR

T1 - Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia

T2 - A GENFI Study

AU - Serpente, Maria

AU - Fenoglio, Chiara

AU - Genetic Frontotemporal Initiative (GENFI)

AU - Arcaro, Marina

AU - Carandini, Tiziana

AU - Sacchi, Luca

AU - Pintus, Manuela

AU - Rotondo, Emanuela

AU - Borracci, Vittoria

AU - Ghezzi, Laura

AU - Bouzigues, Arabella

AU - Russell, Lucy L.

AU - Foster, Phoebe H.

AU - Ferry-Bolder, Eve

AU - Van Swieten, John C.

AU - Jiskoot, Lize C.

AU - Seelaar, Harro

AU - Sánchez Valle, Raquel

AU - Laforce, Robert

AU - Graff, Caroline

AU - Vandenberghe, Rik

AU - De Mendonça, Alexandre

AU - Tiraboschi, Pietro

AU - Santana, Isabel

AU - Gerhard, Alexander

AU - Levin, Johannes

AU - Sorbi, Sandro

AU - Otto, Markus

AU - Pasquier, Florence

AU - Ducharme, Simon

AU - Butler, Chris R.

AU - Le Ber, Isabelle

AU - Finger, Elizabeth

AU - Tartaglia, Maria Carmela

AU - Masellis, Mario

AU - Rowe, James B.

AU - Synofzik, Matthis

AU - Moreno, Fermin

AU - Borroni, Barbara

AU - Rohrer, Jonathan D.

AU - Arighi, Andrea

AU - Galimberti, Daniela

AU - Alberici, Antonella

AU - Afonso, Sónia

AU - Alves, Patricia

AU - Anderl-Straub, Sarah

AU - De Houwer, Julie

AU - Giannini, Lucia

AU - Papma, Janne M.

AU - Poos, Jackie

AU - Van Minkelen, Rick

PY - 2024/8/20

Y1 - 2024/8/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85201894628&partnerID=8YFLogxK

U2 - 10.3233/JAD-240557

DO - 10.3233/JAD-240557

M3 - Article

C2 - 39121124

AN - SCOPUS:85201894628

SN - 1387-2877

VL - 100

SP - S187-S196

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - s1

ER -

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

Abstract

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