Transposable element small RNAs and large RNAs in aging brains and implications in Huntington's and Parkinson's disease.

Transposable elements (TEs) are implicated in aging and neurodegenerative disorders, but the impact on brain TE RNA dynamics in these phenomena is not fully understood. Therefore, we quantify TE RNA changes in aging postmortem human and mouse brains and in the neurodegenerative disorders Huntington's disease (HD) and Parkinson's disease (PD). We track TE small RNAs (smRNAs) to assess the relationship to TE large RNA (laRNA) expression patterns. Human brain transcriptomes from the BrainSpan Atlas display significant shifts of TE smRNA patterns, whereas aging mouse brains lack any TE RNA changes despite a clear shift in aging-associated gene messenger RNA (mRNA) levels. The human frontal cortex displays the most pronounced sense TE smRNAs with a negative relationship between the TE smRNAs and laRNAs indicative of age-associated regulatory effects. Our analysis reveals TE smRNA dysregulation in HD, whereas PD shows a stronger impact on TE laRNAs, potentially correlating with the early average age of death for HD relative to PD. Furthermore, the TE-silencing factor TRIM28 is downregulated in adult human brains, possibly explaining some of these observed TE RNA changes. Our study suggests that the expression of particular TE RNAs may serve as biomarkers of human brain aging and neurodegenerative disorders.