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Alzheimer's disease linked to two new genes, and immune response

24 July 2017

By Caroline Casey

Appeared in BioNews 910

Two new genes which alter the risk of developing Alzheimer’s disease (AD) have been identified.

The study analysed the DNA of over 85,000 people, comparing gene variants between AD patients and healthy volunteers. They identified one gene variant that protected against AD, while another increased risk of developing the disease.

Dr Rebecca Sims at Cardiff University’s School of Medicine, and first author of the study, published in Nature Genetics, said 'these particular genes...are very good targets for potential drug treatment', as they produce proteins that are highly expressed in microglial cells; the resident immune cells of the brain. She added that this data 'suggest that immune cells in the brain play a causal role in the disease'.

'This is direct evidence that if drugs can be designed to target these proteins, we have a chance to alter disease risk in people,' said Professor Gerard Schellenberg, at the University of Pennsylvania's Perelman School of Medicine, and one of the team. 'These multiple gene "hits" all originating from microglia are the clearest demonstration that these cells are part of Alzheimer's pathology and, more importantly, provide clear protein targets where we can start to intervene with drugs.'

Presently, AD affects around 850,000 people in the UK and current treatments have limited effect. The disease causes a build-up of proteins in the brain, which form toxic structures called plaques and tangles. These structures damage the connections between nerve cells, causing them to die. Microglia respond to these dying cells as well as the toxic structures themselves, therefore targeted treatments could be beneficial.

The study also revealed a novel mutation in a third gene, also highly expressed in microglia, which has previously been associated with increasing the risk of AD, called TREM2 (see BioNews 682).

The research has been well received by the AD research community with Dr Doug Brown, director of research and development at the UK's Alzheimer’s Society explaining that 'the discovery of two new risk genes for Alzheimer’s is an exciting advance that could help to deepen our understanding of what happens in the brains of people with the disease'.

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