Scientists have discovered a trio of genetic mutations that account for nearly 100,000 cases of Alzheimer's disease in Britain today.
Three genes that protect the brain from damage and ensure neurons work properly were found to be impaired in many patients with the disease, in the largest genetic study of the condition yet.
The work has been hailed as a "huge step" towards earlier testing and better treatment for Alzheimer's and is the first in 15 years to find new genes associated with the disease.
Previously, scientists knew of only one gene, called APOE4, which increases the risk of developing the most common form of the disease.
"If we were able to remove the detrimental effects of these genes, we could reduce the proportion of people suffering Alzheimer's disease by approximately 20%," said Julie Williams, an Alzheimer's researcher at Cardiff University. "In the UK alone this would prevent just under 100,000 people developing the disease."
About 417,000 people have Alzheimer's disease in Britain, the vast majority of whom have the late-onset form that develops after the age of 65. A very rare form of Alzheimer's disease that runs in families can affect much younger people.
Scientists believe that genes account for 80% of our chance of developing late-onset Alzheimer's, the rest coming from lifestyle and environmental factors.
The newly discovered genes have challenged scientists' thinking on how Alzheimer's disease develops in older people. Patients often suffer inflammation of the brain, an effect that was thought to be a symptom of the disease. But the latest findings suggest that unchecked inflammation may actually play a role in causing the condition.
Scientists believe they will find more genes linked to Alzheimer's that in future could help in assessing a person's risk of developing the disorder.
"This study is a huge step towards achieving an earlier diagnosis of Alzheimer's and improving the lives of the many people affected by the disease," said Sir Leszek Borysiewicz, chief executive of the Medical Research Council, which partly funded the work.
Williams's team conducted a "genome wide association study", in which the genetic codes of nearly 4,000 Alzheimer's patients were compared with the genomes of almost 8,000 healthy individuals.
The researchers found variants of three genes that were risk factors for developing Alzheimer's. One of the genes was APOE4, but the other two had not previously been linked to the disease.
One gene, called clusterin, helps to protect the brain from exessive inflammation caused by infections and other illnesses. The gene is also involved in removing clumps of rogue protein known as amyloid plaques, which are commonly seen in the brains of Alzheimer's patients. Defects in the gene hamper its ability to do these jobs and increase the risk of Alzheimer's.
The second new gene, called Picalm, is crucial for maintaining the health of connections between brain cells. Mutations in the Picalm gene are thought to disrupt the ability of brain neurons to talk to each other and form memories.
A related study of more than 7,000 Alzheimer's patients and healthy volunteers, led by Philippe Amouyel at the National Institute of Health and Medical Research in Lille, also identified a variant of the clusterin gene as a risk factor for the disease.
When the two groups combined their data, they discovered a third new gene called CR1 that was also linked to Alzheimer's disease. The CR1 gene is involved in protecting the brain by clearing out amyloid plaques that can build up in Alzheimer's patients.
The work will enable scientists to start work on drugs that mimic the effects of the healthy genes and so help to prevent Alzheimer's developing in patients who carry mutated variants.
Rebecca Wood, of the Alzheimer's Research Trust, which part-funded the study, said the work was "a leap forward for dementia research".