Primary progressive aphasia (PPA) damages the parts of the brain that control speech and language. There are three clinical PPA variants: nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). The pathophysiology underlying PPA variants is not fully understood, including the role of micro (mi)RNAs which were previously shown to play a role in several neurodegenerative diseases. Using a two-step analysis (array and validation through real-time PCR), we investigated the miRNA expression pattern in serum from 54 PPA patients and 18 controls. In the svPPA cohort, we observed a generalized upregulation of miRNAs with miR-106b-5p and miR-133a-3p reaching statistical significance (miR-106b-5p: 2.69 +/- 0.89 mean +/- SD vs. 1.18 +/- 0.28, p < 0.0001; miR-133a-3p: 2.09 +/- 0.10 vs. 0.74 +/- 0.11 mean +/- SD, p = 0.0002). Conversely, in lvPPA, the majority of miRNAs were downregulated. GO enrichment and KEGG pathway analyses revealed that target genes of both miRNAs are involved in pathways potentially relevant for the pathogenesis of neurodegenerative diseases. This is the first study that investigates the expression profile of circulating miRNAs in PPA variant patients. We identified a specific miRNA expression profile in svPPA that could differentiate this pathological condition from other PPA variants. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort.

miRNA Expression Is Increased in Serum from Patients with Semantic Variant Primary Progressive Aphasia / M. Serpente, L. Ghezzi, C. Fenoglio, F.R. Buccellato, G.G. Fumagalli, E. Rotondo, M. Arcaro, A. Arighi, D. Galimberti. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:15(2022 Jul 30), pp. 8487.1-8487.11. [10.3390/ijms23158487]

miRNA Expression Is Increased in Serum from Patients with Semantic Variant Primary Progressive Aphasia

M. Serpente
Primo
;
C. Fenoglio;F.R. Buccellato;G.G. Fumagalli;E. Rotondo;M. Arcaro;A. Arighi
Penultimo
;
D. Galimberti
Ultimo
2022

Abstract

Primary progressive aphasia (PPA) damages the parts of the brain that control speech and language. There are three clinical PPA variants: nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). The pathophysiology underlying PPA variants is not fully understood, including the role of micro (mi)RNAs which were previously shown to play a role in several neurodegenerative diseases. Using a two-step analysis (array and validation through real-time PCR), we investigated the miRNA expression pattern in serum from 54 PPA patients and 18 controls. In the svPPA cohort, we observed a generalized upregulation of miRNAs with miR-106b-5p and miR-133a-3p reaching statistical significance (miR-106b-5p: 2.69 +/- 0.89 mean +/- SD vs. 1.18 +/- 0.28, p < 0.0001; miR-133a-3p: 2.09 +/- 0.10 vs. 0.74 +/- 0.11 mean +/- SD, p = 0.0002). Conversely, in lvPPA, the majority of miRNAs were downregulated. GO enrichment and KEGG pathway analyses revealed that target genes of both miRNAs are involved in pathways potentially relevant for the pathogenesis of neurodegenerative diseases. This is the first study that investigates the expression profile of circulating miRNAs in PPA variant patients. We identified a specific miRNA expression profile in svPPA that could differentiate this pathological condition from other PPA variants. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort.
circulating miRNAs; gene expression; logopenic variant PPA; semantic variant primary progressive aphasia (svPPA); Brain; Humans; Language; Semantics; Aphasia, Primary Progressive; MicroRNAs
Settore BIO/13 - Biologia Applicata
Article (author)
File in questo prodotto:
File Dimensione Formato  
ijms-23-08487-v2.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.43 MB
Formato Adobe PDF
1.43 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/937363
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact