Study uncovers tau’s role in reversing mitochondrial electron flow, offering new Alzheimer’s drug target

A Stanford-led research team has identified a previously unknown way that the protein tau disrupts cellular function, adding to its status as a leading target in Alzheimer’s drug development.

The scientists discovered that tau interferes with mitochondria by causing electrons to travel backward through the organelle’s electron transport chain, a process called reverse electron transport. This reversal generates reactive oxygen species, leading to cellular stress and inflammation.

In experiments with flies and mice, blocking reverse electron transport mitigated the harmful effects of tau and restored learning and memory performance. Analyses of human laboratory cells and patient brain tissue suggest the mechanism may be relevant in people, though further work is needed to confirm therapeutic potential.