HUNTINGTON’S DISEASE AND EARLYONSET ALZHEIMER’S DISEASE SHARE A TRANSCRIPTOMIC SIGNATURE

Background: Neurodegenerative diseases share progressive loss of neurons and protein misfolding, which ultimately culminates in dementia; many diseases have been identified as causes of early-onset dementia (< 65 years of age) such as Huntington’s disease (HD) and early-onset Alzheimer’s disease (EOAD). Importantly, disease-specific genetic mutations have already been identified for HD and EOAD. Thus, one could suggest that the molecular link between these diseases may arise from alterations at the transcriptomic level, which is yet to be determined. Objective: We aimed at identifying transcriptome similarities between HD and EOAD. Methods: We collected data of the postmortem cerebral cortex from 1 HD and 6 AD microarray studies in the Gene Expression Omnibus. Of note, only subjects with age at death under 65 were selected (HD: n = 158, controls: n = 158; EOAD: n = 65, controls: n = 266). Differential expression and functional enrichment analyses were performed. Results: We identified 1,260 differentially expressed genes and 675 enriched gene ontology terms between HD and EOAD. Conclusion: Our results demonstrate a transcriptomic signature shared by HD and EOAD. Unveiling the similarities between these diseases at the transcriptomic level could advance our knowledge about pathogenesis and may help to develop therapeutic strategies targeting early-onset dementias.