Genetic predictor determines Alzheimer's risk

A new genetic predictor method can identify people at risk of developing Alzheimer's disease, years before symptom onset.

Alzheimer's disease begins in the brain up to 20 years before dementia is diagnosed in patients. With no cure currently available, identifying younger individuals with high risk of developing the disease could aid better recruitment for clinical trials. This study identified a novel computational method to generate an individual's Alzheimer's disease risk score based on pre-existing data. Examining the blood of individuals with high risk, established new potential blood-based biomarkers for Alzheimer's disease.

'We developed a genetic predictor of Alzheimer's disease associated with both clinical diagnosis and age-dependent cognitive decline. By studying the circulating proteome of healthy individuals with very high versus low inherited risk, our team nominated new biomarkers of neurocognitive disease,' said lead author of the study, Dr Amit Khera.

The researchers re-analysed over seven million common DNA variants identified from a previous genome wide associated study of 60,000 people with or without Alzheimer's disease. By understanding which genetic variants are associated with developing Alzheimer's disease, they established a scoring system to robustly identify people with high or low risk.

Putting their risk score to use, the researchers calculated a very high or low risk score for 636 blood donors and analysed if their score correlated with the concentration of any proteins measured in their blood. This experiment identified 27 proteins which significantly correlated with Alzheimer's disease risk, including some not previously associated with the disease.

Although these findings may contribute to improved Alzheimer's disease research, risk scores are not currently used in clinical practice, as no effective therapies are available, and individuals may be subjected to anxiety, as well as high insurance rates.

'By evaluating 7.1 million gene variants, the team developed a more comprehensive genetic risk score for Alzheimer's. This genetic risk score, like others that have been developed previously, is unlikely to be useful for screening people for Alzheimer's or supporting an early diagnosis, but it could help to recruit people with early Alzheimer's into clinical trials,' said Dr Rosa Sancho, head of research at Alzheimer's Research UK.

Further limiting the findings, the individuals profiled in this paper were from European descent, and the risk score may not work well in non-European populations.

The results of this research are published in the journal PLOS Genetics.