Rare genetic mutation in PLD3 gene increases the risk of Alzheimer's disease in later life

A research team from The University of Nottingham has helped uncover a second rare genetic mutation which strongly increases the risk of Alzheimer's disease in later life.
Researchers pinpointed a rare coding variation in the Phospholipase D3 ( PLD3 ) gene which is more common in people with late-onset Alzheimer's than non-sufferers.

The discovery is an important milestone on the road to early diagnosis of the disease and eventual improved treatment. Having surveyed the human genome for common variants associated with Alzheimer's, geneticists are now turning the spotlight on rare mutations which may be even stronger risk factors.

More than 820,000 people in the UK have dementia and the number is rising as the population ages.

Nottingham's genetic experts have been working with long-term partners from Washington University, St Louis, USA and University College, London, to carry out next-generation whole exome sequencing on families where Alzheimer's affects several members.

The collaboration uncovered the first ever rare genetic mutation implicated in disease risk, linking the TREM2 gene to a higher risk of Alzheimer's ( published in the New England Journal of Medicine ).
In a new study published in the Nature, the researchers have revealed that after analysis of the genes of around 2,000 people with Alzheimer's, a second genetic variation has been found, in the PLD3 gene.

PLD3 influences processing of amyloid precursor protein which results in the generation of the characteristic amyloid plaques seen in AD brain tissue, suggesting that it may be a potential therapeutic target.

The researchers used Nottingham's Alzheimer's Research UK DNA bank, one of the largest collections of DNA from Alzheimer's patients, to completely sequence the entire coding region ( exome ) of the PLD3 gene.
The results showed several mutations in the gene occurred more frequently in people who had the disease than in non-sufferers.
Carriers of PLD3 coding variants showed a two-fold increased risk for the disease. ( Xagena )

Source: University of Nottingham, 2013


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