A Single-Nucleus RNA Sequencing Analysis of HERVs and LINE1s in Alzheimer's and Parkinson's Disease

Sammanfattning: Transposable elements (TEs) are mobile genetic elements that make up roughly 50% of the human genome, with retrotransposons (or transposons which retrotranspose via an RNA intermediate) making up the vast majority of these elements. Recent studies have suggested that TEs could play a role in many neurological conditions, including ALS and dementia. The specific reasons why TEs are associated with these conditions remain somewhat unclear, with potential explanations including mutagenic insertion, immune responses to the presence of transcripts, and cytotoxic peptides resulting from the translation of these transcripts. We sequenced single-nuclei RNA sequencing (snRNA-seq) to profile the impact that TEs have on the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Our results show clear evidence for activated microglia and reactive astrocytes in PD, suggesting neuroinflammation. Additionally, using trusTEr, a new bioinformatics pipeline for the quantification of TE expression from single nuclei sequencing datasets, we were able to identify cell type-specific expression patterns of LINE1s and HERVs between diseased and control brains, which raise questions about the functional consequences of an aberrant expression of TEs in the human brain and their role in neuroinflammation.