The largest genetic study of Alzheimer's to date has provided compelling evidence that the disease can disrupt the brain's immune system.
The study used the genomes of 100,000 people with Alzheimer's and 600,000 healthy people and found 75 genes that were linked to an increased risk of the disease.
The findings suggest that over aggressive activity in the brain's immune cells could be the cause of dementia.
Prof Julie Williams is the director of the UK Dementia Research Institute and a co-author of the study.
She said that it was an enormous clue to what was going wrong. The genetics have refocused us.
The study, the largest of its kind to date, allowed scientists to create a genetic risk score that could predict which patients with cognitive impairment would go on to develop Alzheimer's within three years.
The score is not intended for clinical use at the moment, but could be used when recruiting people for trials of drugs aimed at treating the disease in the earliest stages.
Alzheimer's disease is the most common cause of dementia in the UK. There have been no new drugs for the disease in the past two decades, with the exception of Aducanumab, which is currently unavailable in Europe and the UK.
While lifestyle factors such as smoking, exercise and diet can influence Alzheimer's risk, the disease risk is based on genetics. Drug development was influenced by the study of families with rare genetic defects.
The genetics of common disease are highlighted in the latest work.
The risk genes highlighted in the study affect how efficiently the brain's immune cells are used. These cells appeared to be working too hard in people at risk.
A similar pattern was found for genes that control how readily synapses connect. The high-risk variant may have caused the brain to purge connections at a quicker rate.
I'm pretty confident that there are treatments that will work for some of the systems we're looking at.
The findings in the journal Nature Genetics fit with previous results that pointed to a role for the immune system. People with diabetes, which affects the immune system, are at a higher risk of developing dementia, as well as infections that can lead to more rapid cognitive decline.
The director of research at Alzheimer's Research UK said that creating an extensive list of Alzheimer's disease risk genes is like having the edge pieces of a puzzle. The research shows how complex Alzheimer's is, with several different mechanisms implicated in the development of the disease.
The Centre for Discovery Brain Sciences at the University of Edinburgh was not involved in the work.
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