Tau identified as cause of Alzheimer's

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Plaque has long been considered a prime suspect behind Alzheimer's disease. But new findings are causing some investigators to cite tau instead.

“We believed for almost 100 years that [amyloid-beta] plaques are the main culprit in Alzheimer's disease,” study senior investigator Charbel E-H Moussa said. “This study shows it's another protein — a very, very important one, called tau, that is basically the main guilty one.”

Neuronal death happens when tau, found inside neurons, fails to function. Tau's role is to provide a structure — like a train track — inside brain neurons that allows the cells to clear accumulation of unwanted and toxic proteins.

He says his study suggests the remaining Abeta inside the neuron (that isn't pushed out) destroys the cells, not the plaques that build up outside. “When tau does not function, the cell cannot remove the garbage, which at that point includes Abeta as well as tangles of nonfunctioning tau, and the cell dies. The Abeta released from the dead neuron then sticks to the plaque that had been forming.”

Moussa's experiments in animal models also show less plaques accumulates outside the cell when tau is functioning; when tau was reintroduced into neurons that did not have it, plaques did not grow.

Full findings appear in the journal Molecular Neurodegeneration.

Malfunctioning tau can occur due to errant genes or through aging. As individuals grow older, some tau can malfunction while enough normal tau remains to help clear the garbage. In these cases, the neurons don't die, he says. “That explains the confusing clinical observations of older people who have plaque build-up, but no dementia,” Moussa says.

The researcher has long sought a way to force neurons to clean up their garbage. In this study, he shows that nilotinib, a drug approved to treat cancer, can aid in that process. Nilotinib helps the neuron clear garbage, but requires some functional tau, he says.

“The common culprit is tau, so a drug that helps tau do its job may help protect against progression of these diseases,” Moussa added. n


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