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

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.

Automated summary

The study investigates the expression profile of circulating miRNAs in different variants of Primary Progressive Aphasia (PPA). The results show a specific miRNA expression profile in semantic variant of PPA that could differentiate it from other PPA variants. The target genes of these miRNAs are involved in pathways relevant to the pathogenesis of neurodegenerative diseases.