Study uncovers how transposable elements in Alzheimer's-affected brains could hold the key to new therapeutic approaches, as scientists uncover the genetic links behind these molecular disruptions. Study: Widespread transposable element dysregulation in human aging brains with Alzheimer's disease . Image Credit: Tushchakorn / Shutterstock.
com A recent Alzheimer’s and Dementia journal study characterizes transposable element (TE) expression dysregulation by using CRISPR interference (CRISPRi) assays to experimentally identify TEs associated with Alzheimer’s disease (AD). What are TEs? TEs, wlso known as transposons, viral elements, or jumping genes, constitute about 45% of the human genome. Epigenetic mechanisms, such as histone modifications and DNA methylation, can transcriptionally silence TEs.
The functional significance of TEs significantly declines with aging and in patients with neurodegenerative disorders, such as AD. Previous studies using human postmortem brain tissues and Drosophila melanogaster models have reported that tau protein triggers TE activation, which is linked to active chromatin signatures at multiple endogenous retrovirus (ERV) genomic loci. TE activation is also crucial during neurodevelopment, which suggests that brain TE regulation is a common feature across the human lifespan.
During mouse brain development, higher ERV levels in neurons have been associated with inflammatory responses and activated microglia. Depression of long-terminal repeat .
