Transcriptomic Biomarkers for Huntington's Disease: Are Gene Expression Signatures in Whole Blood Reliable Biomarkers?

Huntington's disease (HD) is a severe neurodegenerative disorder manifesting as progressive impairment of motor function, cognitive decline, psychiatric symptoms, and immunological and endocrine dysfunction. We explored the consistency of blood transcriptomic biomarkers in HD based on a novel Slovene patient cohort and expert review of previous studies. HumanHT-12 v4 BeadChip microarrays were performed on the whole blood samples of a cohort of 23 HD mutation carriers and 23 controls to identify differentially expressed (DE) transcripts. In addition, we performed an expert review of DE transcripts identified in comparable HD studies from whole blood, to identify any consistent signature of HD. In the Slovene cohort, we identified 740 DE transcripts (p < 0.01 and a false discovery rate (FDR) of <0.1) of which 414 were downregulated and 326 were upregulated. Pathway analyses of DE transcripts showed enrichment for pathways involved in systemic, rather than neural processes in HD. With an expert review of comparable studies, we have further identified 15 DE transcripts shared by 3 studies. We suggest transcriptomic changes in blood reflect systemic changes in HD pathogenesis, rather than being a direct result of the neuropathological processes in the central nervous system during HD progression, and thus, have limited value as disease biomarkers.