Epigenome-Wide Association Study of the Interaction between Alzheimer’s disease and Systemic Infection

Although most Alzheimer’s disease (AD) cases are sporadic, with no known aetiology, the onset and progression of the disease has been widely linked with inflammation both in the periphery and within the brain. Indeed, many AD sufferers ultimately die with a systemic infection, and infections during life can increase the risk of developing dementia and the rate of cognitive decline in AD patients. However, the mechanistic pathways linking inflammatory processes to AD onset and progression are not known. This study will use an epigenomic approach to elucidate the molecular mechanisms involved in the brain in AD following systemic inflammation. A better understanding of the neurobiological pathways altered in AD during systemic inflammation could ultimately identify new pharmacological targets, potentially improving the lives of millions of AD sufferers worldwide. This work identifies molecular mechanisms that are altered in AD brain during systemic inflammation, which can then be functionally characterised and targeted in in vitro modelling systems. We aimed to profile the genomic DNA methylome of prefrontal cortex brain tissue of Alzheimer’s disease and control patients with and without infection present at the time of death. DNA methylation was analysed in a cohort of 242 samples, including 131 AD patients (n=68 with infection) and 111 control participants (n= 47 with infection); using the Infinium Methylation EPIC array.