The risks of early-life X-ray exposure: A view on brain aging and Alzheimer’s disease pathology
Nowadays, hot topic for many research groups is finding treatment options for the complex and progressive neurodegenerative disorder, Alzheimer’s disease (AD). Equally important, however, is finding the initial inducers of AD, which remain largely elusive and is often subject to debate. The major risk factor for AD is unarguable ageing, which is proposed to be accelerated by ionizing radiation exposure. Epidemiological and animal studies have shown that the developing, immature brain is more sensitive to ionizing radiation exposure compared to the adult brain. Despite the clear common features between radiation-induced changes and an ageing phenotype in the CNS, the mechanisms of childhood irradiation to induce cognitive impairment, and possibly AD, still need to be explored. To this end, we will use both primary hippocampal cultures, as well as a transgenic mouse model predisposed to AD, in which ageing and AD progression after X-ray exposure can be studied within a limited time span. Furthermore, the exact molecular players responsible for radiation-induced ageing and an increased AD risk will be identified by gene expression analysis and validated with loss-of-function approaches. Ultimately, this project will be an important step forward in a better understanding of AD pathology and primary risk factors. On top, our results will be crucial for pediatric patients exposed to X-rays, to ensure a good follow-up and to ultimately increase their quality of life.