Neurology Central

Ask the Experts: the genetics of Alzheimer’s disease (Part 2: Current research, challenges and ethical concerns)

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In line with World Alzheimer’s Month this September, we’ve brought together a panel of experts to discuss the genetics of Alzheimer’s disease in a 3-part debate. How much do genetics contribute to Alzheimer’s risk? What are the research priorities in this field? And could routine genetic screening and personalized treatments one day be a reality for patients? With Alzheimer’s now classed as the most feared disease in the aging global population, our experts address these questions and more. Together bringing insights from across research, social and charity perspectives, our experts are Kevin Morgan (University of Nottingham, UK), Rita Guerreiro (UCL, UK) and Clare Walton (Alzheimer’s Society, UK).
You can read the second installment of the debate below, which focuses on current research priorities, challenges and ethical concerns.
Catch up on Part 1, covering the contribution of genetics to Alzheimer’s risk, the differences between early- and late-onset disease, and how new technologies have advanced our understanding of this ever-expanding field, here. You can also now read the third and final installment here, which looks ahead at future research trends and the potential for personalized medicine.

How much research is currently focused on the genetic basis of Alzheimer’s disease (AD)? Do you think this enough?

Kevin Morgan: I think that there is a general belief in the Alzheimer’s research community that having successfully found a number of associations (currently just under 30) that the genetics has been done. This is not helped by the fact that GWASs of increasing size, whilst pulling out more associations, are showing that the contribution of new loci is becoming increasingly smaller. This has resulted in some questioning the utility of such small effect sizes. However, current bio-informatic approaches such as burden analysis and polygenic risk score (PRS) are beginning to show that summing these small effects can make a significant contribution. This is well illustrated by current PRS estimates, which take into account the contribution of the entire genome to disease pathogenesis. Recent PRS studies have shown that in reality there might well be hundreds, if not thousands, of genes that contribute to an individual’s risk of getting disease. This infers that we are still some way off a total catalogue of genes and that it is rather premature to believe that our understanding is complete.

Rita Guerreiro: There are several large projects currently ongoing and focused on the identification of novel genes and genetic variants associated with AD. These are mainly using whole-exome and whole-genome sequencing data to study large cohorts of cases and controls, as well as families in which AD segregates in several generations but where no mutations in the known AD genes have been identified. Increasing the number of studies looking into the genetic basis of AD can bring positive outcomes, as more researchers will be dedicated to this question. Another important factor will be to increase the numbers of samples studied; the easiest way to do this is through collaboration and sharing of data.

In which area is there the greatest need for more research in the field of AD genetics?

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