Comparisons Between Young, Aged, and Alzheimer's Brains Reveal Specific Expression Patterns for a Subset of Transposons and Satellite Repeats

Abstract

Recent studies have highlighted the involvement of repeat-derived transcripts in the pathological transcriptome of Alzheimer's disease (AD). However, it remains unclear whether these transcripts arise as a consequence of aging or are directly associated with AD pathology. Particularly, the specific contribution of satellite repeats to this phenomenon has not been systematically investigated. In this study, we profiled the non-coding expression patterns of all repetitive DNA elements - including satellites - across healthy young, healthy aged, and aged AD brain samples. Comparative transcriptome analysis revealed only a single differentially expressed repeat between aged and young brains. In contrast, AD brains exhibited significant expression changes in eight specific repeat elements relative to their healthy aged counterparts. Among these AD-specific repeats, the satellite repeat HSATII showed the highest fold change and a modest increase in histone acetylation levels, suggesting potential regulatory or feedback mechanisms in AD pathology. Weighted Gene Co-Expression Network Analysis (WGCNA) identified modules of co-expressed genes and repeats, revealing a network moderately correlated with the AD phenotype and indicating complex interactions between repeats and genes during disease onset. Collectively, our comprehensive analysis of repeat expression in post-mortem human AD brains demonstrates alterations in transposon and satellite repeat expression patterns that are distinct from age-related changes