Scientists have pinpointed a specific part of the brain where Alzheimer's begins and traced how the disease spreads.
High resolution brain scans of 96 healthy adults over the age of 65 revealed the first footprint of Alzheimer's in a dozen individuals who went on to experience symptoms.
Reduced metabolic activity was seen in the lateral entorhinal cortex (LEC), a small region linked to the hippocampus where long-term memories are stored.
The change, associated with declining memory, occurred at a time when all 12 volunteers were free of dementia and was not seen in the 84 participants who did not develop Alzheimer's.
The study also showed how over time the effects of Alzheimer's spread from the LEC to other areas of the brain's cerebral cortex.
One region especially targeted was the parietal cortex, an area involved in various functions including spatial orientation and navigation.
Lead researcher Professor Scott Small, director of the Alzheimer's Disease Research Center at Columbia University in New York, said: "It has been known for years that Alzheimer's starts in a brain region known as the entorhinal cortex. But this study is the first to show in living patients that it begins specifically in the lateral entorhinal cortex, or LEC.
"The LEC is considered to be a gateway to the hippocampus, which plays a key role in the consolidation of long-term memory, among other functions. If the LEC is affected, other aspects of the hippocampus will also be affected."
The scientists suspect Alzheimer's spreads through a kind of neural domino effect. Neurons are first compromised in the LEC, which in turn reduces the integrity of their neighbours.
Two of the hallmarks of Alzheimer's disease are sticky protein deposits in the brain called beta amyloid plaques, and "tangles" of tau protein.
A first step to accumulating beta amyloid is the production of amyloid precursor protein (APP).
"The LEC is especially vulnerable to Alzheimer's because it normally accumulates tau, which sensitises the LEC to the accumulation of APP," said co-author Professor Karen Duff, also from Columbia University.
"Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer's."
Tests on mice confirmed that the same changes in the LEC seen in the volunteers were associated with raised tau and APP.
A high-resolution form of functional magnetic resonance imaging (fMRI) was used to map metabolic activity in the brains of the study participants, all enrolled in the Washington Heights-Inwood Columbia Ageing Project (Whicap).
"Now that we've pinpointed where Alzheimer's starts, and shown that those changes are observable using fMRI, we may be able to detect Alzheimer's at its earliest preclinical stage, when the disease might be more treatable and before it spreads to other brain regions," said Prof Small.
The new imaging method could also be used to assess potential new drug treatments at early stages of the disease, said the researchers.