>Cardiff University in Alzheimer’s genetic discovery

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Scientists have discovered five gene variants that raise the risk of Alzheimer’s disease in work that casts fresh light on the devastating condition.

The research brings the known number of genes associated with Alzheimer’s to 10, which together account for about 300,000 cases of the disease in Britain today.

The findings raise the prospect of earlier testing and better treatments for a condition that costs the UK £23bn a year in long-term care and lost productivity, according to a dementia report commissioned last year by the Alzheimer’s Research Trust.

Scientists discovered the five genes after comparing the genetic makeup of tens of thousands of patients with those of healthy volunteers. Genes account for 60 to 80% of our chance of developing late-onset Alzheimer’s, the rest coming from lifestyle and environmental factors. Having high blood pressure in middle age is known to raise the risk of developing Alzheimer’s later in life.

The work is described in two studies published in Nature Genetics, led by Julie Williams at Cardiff University’s MRC Centre for Neuropsychiatric Genetics, and Gerard Schellenberg at the University of Pennsylvania School of Medicine in Philadelphia.

The emerging picture of Alzheimer’s is a disease driven by subtle genetic factors whose effects build up throughout life and ultimately cause the steady and irreversible destruction of brain cells. The vast majority of patients have late-onset Alzheimer’s disease, which develops after the age of 65. A very rare form of Alzheimer’s disease that runs in families can affect much younger people.

“If we could eliminate the detrimental effects of all 10 variants, we would eliminate 60% of Alzheimer’s disease,” Williams said.

Patients with Alzheimer’s disease are more likely to have versions of genes that affect the immune system and the way their brains deal with cholesterol, and proteins that form plaques and tangles around nerve cells. The latest research describes genes that govern how cells absorb and use molecules, a process not linked to the disease before.

“What this work is doing is focusing our research. It is telling us where we should be looking,” Williams said.

By understanding how genes cause Alzheimer’s disease, scientists hope to identify drugs or lifestyle changes that can counteract their ill effects and stave off the condition.

“In 10 to 15 years we might be taking a number of preventative drugs to avoid the onset of Alzheimer’s disease just as we now take statins to prevent heart disease,” Williams said.

The research highlights the difficulty that can arise when genes implicated in incurable diseases are discovered. Williams said scientists know too little about Alzheimer’s genes to judge whether a person will get the disease or not. But when James Watson, the genetics pioneer who co-discovered the double helix of DNA half a century ago, had his genome sequenced in 2007, the one gene left out was APOE, one of the strongest predictors of Alzheimer’s disease.

Susanne Sorensen, head of research at the Alzheimer’s Society, said: “By 2021, one million people will develop dementia and yet the government still spends eight times less on dementia research than cancer research.”

In the next phase of the work, Williams plans to use next generation genome sequencing machines that can read every letter of a person’s genetic makeup to search for probably tens of other genes that contribute to Alzheimer’s disease, including those that are rare or only marginally raise the risk of developing the condition.