Study Rationale:
Many people assume that most of our DNA is made up of genes, but in fact, genes account for only about 2% of the human genome. More than half is made up of transposable elements (TEs), often called “the dark matter of the genome” because they are difficult to study. As a result, their role in health and disease remains largely unknown. Our recent work in the ASAP initiative has linked TEs to Parkinson’s Disease (PD) inflammation and disease progression. Aging is the main risk factor for PD and patients experience a quicker ageing process. This project explores how aging and PD differ at the molecular level, and how TEs may contribute to the development and progression of PD.
Hypothesis:
We hypothesize that PD and ageing affect a large part of our DNA (TEs) in a way that eventually leads to age-associated and PD-associated neuroinflammation.
Study Design:
We will perform new molecular techniques in human brain tissue collected by the ASAP Collaborative Research Network. This will produce unique, unprecedented data capturing both DNA and RNA of each cell that will allow us to research TEs. We will analyze how TEs are affected in the brain as people age and compare this between healthy individuals and those with PD. We will also look at which cell types show the biggest changes, where in the brain these changes happen, and finally, how this might affect surrounding cells.
Impact on Diagnosis/Treatment of Parkinson’s disease:
By revealing how TEs change with aging and in PD, and how this affects brain cells, we begin to unlock the “dark matter” of the genome. This has the potential to redefine our knowledge on human ageing, PD, and may lead to new therapeutic targets to slow the progression of the disease.
Next Steps for Development:
If successful, this research will provide new tools to study TEs, along with a detailed map of how TEs are affected in the aging and PD brain. These results will guide future mechanistic studies and support the development of new therapies.