One study, by Karen Duff and Dr. Scott A. Small and their colleagues at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center, was published on Wednesday in the journal PLoS One. The other, by Dr. Bradley T. Hyman, director of the Alzheimer’s Disease Research Center at Massachusetts General Hospital, and his colleagues, is to be published in the journal Neuron.

Both groups of researchers were inspired by the many observations over the years that Alzheimer’s starts in the entorhinal cortex and spreads.

But, said Dr. Small, “what do we mean by ‘spreads?’ ”

Researchers knew that something set off Alzheimer’s disease. The most likely candidate is a protein known as beta amyloid, which accumulates in the brain of Alzheimer’s patients, forming hard, barnaclelike plaques. But beta amyloid is very different from tau. It is secreted and clumps outside cells. Although researchers have looked, they have never seen evidence that amyloid spreads from cell to cell in a network.

Still, amyloid creates what amounts to a bad neighborhood in memory regions of the brain. Then tau comes in — some researchers call it “the executioner” — piling up inside cells and killing them. If some cells take longer than others to succumb to the bad neighborhood, that would explain the spread of the disease in the brain, and there would be no need to blame something odd, like the spread of tau from cell to cell.

Studies in humans, though, could not determine whether that hypothesis was correct. They involved autopsy and brain imaging studies and were “indirect and inconclusive,” Dr. Small said.

Looking at the brains of people who have died of the disease, Dr. Duff said, is like looking at a wrecked car and trying to figure out the accident’s cause. Faulty brakes? Broken struts?

The question of which hypothesis was correct — tau spreading cell to cell, or a bad neighborhood in the brain and cells with different vulnerabilities to it — remained unanswerable. Dr. Hyman said he tried for 25 years to find a good way to address it. One of his ideas was to find a patient or two who had had a stroke or other injury that severed the entorhinal cortex from the rest of the brain. If the patient developed Alzheimer’s in the entorhinal cortex — and it remained contained there — he would have evidence that the disease spread like an infection. But he never found such patients.