Changes in the brain and substances in the fluid surrounding the spinal column can be found in people who will develop inherited Azheimer's disease decades before symptoms will develop, and earlier than previously thought.
At this very early stage drugs designed to halt the progression of the condition are likely to be more effective than once memory problems have taken hold, the researchers said.
They made the discovery by testing a small group of people with a genetic fault that means they are certain to develop a rare form of early-onset Alzheimer's.
Before they showed signs of memory problems, or characteristic plaques in the brain associated with the disease, the team found these people had structural differences in parts of the brain and larger quantities of protein in their cerebrospinal fluid than people without the genetic fault.
They hope this means tests can be developed to predict which people will go on to suffer from Alzheimer's in the general population.
The findings were published in the journal Lancet Neurology and follow an announcement by David Cameron that a series of NHS clinics will be established to use brain scans and memory tests to diagnose Alzheimer's disease earlier.
The research team from the Banner Alzheimer's Institute in Phoenix, Arizona and elsewhere, studied 44 people aged between 18 and 26, 20 of whom carried the PSEN1 mutation for the disease.
Those with this mutation develop Alzheimer's disease around age 45 but they found that at this early age they had greater activity in certain regions of the brain, less grey matter in those parts and higher levels of amyloid beta protein in their cerebrospinal fluid. This protein is known to build up in 'plaques' in the brain and is a tell-tale sign of Alzheimer's.
Lead author Prof Eric Reiman said: “These findings suggest that brain changes begin many years before the clinical onset of Alzheimer’s disease, and even before the onset of amyloid plaque deposition.
"They raise new questions about the earliest brain changes involved in the predisposition to Alzheimer’s and the extent to which they could be targeted by future prevention therapies.”
The same team conducted another study and found that plaque build-up begins in the brains of people with the PSEN1 mutation in their 20s.
Led by Dr Adam Fleisher, of the Banner Alzheimer’s Institute, the study included 50 mutation carriers and non-carriers aged 20 – 56. It was hoped the finding could help prevent the condition in people with the mutation.
In an accompanying editorial Professor Nick Fox of the Institute of Neurology at University College London, said: “These findings question our models of Alzheimer’s disease on several fronts.
"They suggest that neurodegenerative changes occur over 20 years before symptom onset and somewhat earlier than was suggested by previous brain imaging studies of individuals at risk of inherited Alzheimer’s disease.
"Further research is needed, but one interpretation of these results might be that they add to the accumulating evidence that Alzheimer’s disease is characterised by a long presymptomatic period of slowly progressive changes that can potentially be tracked, thereby opening up a therapeutic window for early intervention.”