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Genetic risk scores could predict Alzheimer's

11 July 2016
Appeared in BioNews 859

Researchers looking at multiple genes have developed risk scores that could identify those most likely to develop Alzheimer's disease in later life.

They also claim to have identified small differences in brain structures in those aged 18–35 years that are correlated with the highest risk scores.

'The stage of Alzheimer's before symptoms show up is thought to last over a decade,' said Dr Elizabeth Mormino of Massachusetts General Hospital, lead author of the study. 'Given that current clinical trials are testing whether therapies can slow memory and thinking decline among people at risk for the disease, it is critical to understand the influence of risk factors before symptoms are present.'

The study, published in Neurology, investigated the relationship between genetic variants associated with a risk of developing Alzheimer's disease and with cognitive function, memory performance, and size of the hippocampus – a brain structure involved in memory. They looked at both older adults without dementia as well as younger adults with normal cognitive function.

Alzheimer's disease is highly heritable and is known to be associated with genes such as APOE. But other common genetic variants may collectively account for as much as 25 percent of an individual's predisposition for developing Alzheimer's disease, according to the study, and could influence mechanisms associated with Alzheimer's long before the onset of disease.

The research team created their polygenic risk score using information from the International Genomics of Alzheimer’s Project (IGAP) Genome Wide Association Study. They investigated 166 people with dementia as well as 1026 older people without dementia.

They found that older adults without dementia but who had higher polygenic risk scores had worse memory performance and smaller hippocampal volumes than those with low risk scores. Over time they also experienced a greater deterioration of memory. Over three years, 15 of 194 participants developed mild cognitive impairment or Alzheimer's disease, and 143 out of 332 participants with mild cognitive impairment went on to develop Alzheimer's disease.  

The team also tested whether traits associated with Alzheimer's disease could be identified early on in life. Among 1322 younger adults aged between 18 and 35 years, a higher risk score was associated with a smaller hippocampus. Although it only accounted for 0.2 percent of the difference in hippocampus volume between those with high and low risk, the researchers say that it suggests that genetic risk may be detectable in young adults long before the onset of clinical symptoms. 

'Our study was small, and larger numbers of participants will need to be studied to confirm our findings,' said Dr Mormino.

Dr Doug Brown, director of research at the Alzheimer’s Society, said: 'This study provides evidence that creating a "risk score" could possibly be used to predict whether someone has a higher chance of developing memory problems, [but there is] a huge challenge in making sure that they can accurately predict a person's risk.'

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