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: "This study is the first to show in living patients that it begins specifically in the 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.
The new imaging method could also be used to assess potential new drug treatments at early stages of the disease, said the researchers.