Tau protein disrupts energy supply in brain cells

Tau is a protein that normally helps maintain the structure of brain cells. In Alzheimer’s and several related brain diseases, it misfolds and aggregates into tangles that damage cells. For a long time, those tangles were thought to harm cells mainly by blocking internal transport. New research now points to an additional mechanism. The study, published in the journal Science, presents evidence that tau can directly impair the mitochondria, the energy-producing structures inside cells.

Mitochondria generate the energy brain cells need to function. They are especially sensitive to damage, and neurons are particularly dependent on them because of their high energy demands. If tau disrupts mitochondrial function, that could help explain why brain cells in Alzheimer’s decline so rapidly, even before tau tangles reach a large size.

A direct hit on cellular energy

The researchers found evidence that tau binds to components of the mitochondria and interferes with their operation. Energy output drops, and the cell enters a state of energy deficit. That makes it more vulnerable to additional stress and can ultimately lead to cell death.

This finding has implications for how Alzheimer’s treatments are developed. Most existing therapies target tau tangles directly, aiming to remove them or prevent their formation. But if tau causes mitochondrial damage earlier in the disease process, before large tangles are visible, that could represent a separate therapeutic target worth pursuing.

Early-stage research

The findings are largely based on cell and animal models. How this plays out precisely in human brain tissue, and whether improving mitochondrial function could compensate for tau-related damage, has not yet been demonstrated. The authors present this as a newly identified mechanism warranting further investigation, not a clinical approach already available.

Read the original article