Scientists have pinpointed a way the Alzheimer’s-linked protein tau damages brain cells: it slips inside the cell’s power plants and makes their energy machinery run in reverse.
Researchers at Stanford University School of Medicine and the University of California, San Francisco found that hyperphosphorylated tau — the abnormal form that builds up in Alzheimer’s — enters mitochondria and binds a component of the electron transport chain called NDUFS3. That warps the machinery, causing reverse electron transport that spews out damaging reactive oxygen molecules, feeding a self-perpetuating cycle of injury. The work appeared August 6, 2026 in Neuron.
Seen across many models
The team observed the effect in fruit flies, mice, human brain tissue, cultured neurons and patient-derived stem cells — and suggests the mechanism may link tau to mitochondrial dysfunction across several diseases. “This is the first demonstration of exactly what tau does inside mitochondria,” said Stanford’s Bingwei Lu.
A possible drug target
Crucially, an experimental compound (called CPT) prevented tau from binding NDUFS3, blocking the reverse electron flow without disrupting normal energy production — and improved behavior in animal models. It is early, preclinical work, but it points to a fresh, specific target for future Alzheimer’s therapies.