PhD Project – SC funded by NSG – Using the BDR Resource to understand the Genetics of Alzheimer’s.
The Brains for Dementia Research (BDR) project is an initiative funded jointly by the Alzheimer’s Society and Alzheimer’s Research UK to address the shortage of brain tissue from individuals that is essential for research into dementia (http://www.brainsfordementiaresearch.org.uk/). The BDR project engages participants that have different types of dementia as well as individuals that do not have dementia to investigate how and why dementia occurs.
Dementia has been shown to have a genetic aspect as to why it develops, and previous research has identified numerous genetic variants that are associated with developing dementia. Therefore, with the establishment of the BDR sample it is vital that DNA is extracted from each participant and investigated for these genetic variations. Our laboratory is funded to extract the DNA from these BDR samples and ‘genotype’ it, investigating the genetic variants for association with dementia. Due to advances in technology, we have been able to look at almost 500,000 genetic variants in 1187 BDR participants and implement a new type of analysis called “Polygenic Risk Score (PRS)”. The PRS looks at all the genetic variants an individual has and estimates how frequently each variant is found in dementia, and how much each variant increases (or decreases) your risk of developing dementia. The PRS then adds up the total genetic risk from all the variants a person has and creates a ‘score’. We have shown that people with dementia have higher PRS than those without dementia and based on the PRS with can predict with 82.5% accuracy who is likely to develop dementia. We have made this data available to other researchers via the DPUK, so they can use the data for different analyses without having to use up more brain tissue to extract DNA and repeat the genotyping.
It is hoped that the PRS will not only be able to judge a persons’ risk for developing dementia, but also differentiate more accurately between the causes of dementia, such as Alzheimer’s disease, Vascular and Lewy Body Dementia. In addition, we believe that further research with the PRS will lead to the identification of specific biological pathways that are malfunctioning in dementia and will therefore lead to new therapeutic interventions. It is possible that in the future, the PRS analysis will be used to predict who will be at high risk of developing dementia and pave the way towards personalized treatments dependent on the genetic variants present so that the onset of dementia is delayed or even prevented entirely.