Shared transcriptomic signature between Huntington’s disease and early‐onset Alzheimer’s disease

• Published in: Alzheimer's & dementia Vol. 17; pp. e053759 - n/a
• Main Authors: Carello‐Collar, Giovanna, De Bastiani, Marco Antônio, Zimmer, Eduardo R.
• Format: Journal Article
• Language: English
• Published: United States 01.12.2021
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.053759

Background Neurodegenerative diseases share common pathological features, including progressive loss of neurons and protein misfolding, which ultimately culminates in dementia. Interestingly, dementia is not restricted to elderly people. In fact, 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 EOAD and HD. Thus, one could suggest that the molecular link between EOAD and HD may arise from alterations at the transcriptomic level, which is yet to be determined. In keeping with this, we hypothesized that EOAD and HD share a transcriptomic signature. In this work, we aimed at identifying transcriptome similarities between both diseases. Method We collected data sample of postmortem cerebral cortex from 6 AD (GSE33000, GSE118553, GSE122063, GSE39420, GSE44770, GSE44771) and 1 HD (GSE33000) microarray studies in the Gene Expression Omnibus, a public transcriptomic data repository. Of note, only subjects with age at death under 65 were selected (EOAD: n = 65, controls: n = 266; HD: n = 158, controls: n = 158). Differential expression and functional enrichment analyses were performed for each group versus their respective age‐matched controls. Result We identified 1,260 differentially expressed genes (476 up‐ and 784 down‐regulated genes) and 675 enriched gene ontology (GO) terms between EOAD and HD. The GO terms were grouped in 11 clusters of biological processes (Table 1). Cluster observation suggests a link in the apoptotic signaling, immune response and synaptic transmission processes in both diseases. Conclusion Our results demonstrate a transcriptomic signature shared by EOAD and HD. Unveiling the similarities between EOAD and HD at the transcriptomic level could advance our knowledge about the pathogenesis of these diseases and may help developing therapeutic strategies targeting early‐onset neurodegenerative diseases.