Neurology Central

Ask the Experts: the genetics of Alzheimer’s disease (Part 1: Introduction to Alzheimer’s genetics)

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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).
Take a look at the first installment of this debate below, looking at 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.
You can now also read Part 2 and Part 3, which delve deeper into research priorities, the pros and cons of genetic screening, and the potential for personalized medicine.

How much of a role do genetics play in the onset and development of Alzheimer’s disease (AD)?

Kevin Morgan: All complex diseases are a mixture of environment and genetics and their position on this spectrum varies due the relative contribution of each. In the case of AD we know that there is a substantial genetic component and that this is by far the biggest contributor to disease risk. Depending on who you talk to, the genetic component in Alzheimer’s has been estimated to be in the region of 70% to 80%; however, this still leaves a sizable environmental component of 20% to 30% about which we know little. In addition, the interplay between genes and the environment, as indeed between genes (epistasis), is likely to impact on the disease process and is an area in which we need to increase our understanding.

Clare Walton: We don’t have definite answer for this, but estimates range from about 50–80% of an individual’s risk being determined by genetics. Some cases of AD are inherited but these are rare and account for fewer than 1% of all cases. Most cases are sporadic and not inherited, but we now know of about 30 gene variants that can increase or decrease a person’s risk of developing AD.

Is there a significant difference between genetic contributions in different variants of the disease, for example, early or late onset?

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