Human Brain Proteins Made Mouse Proteins Fold the Same Way

A British and Japanese team reports that tau filaments taken from the brains of people who had Alzheimer's disease or corticobasal degeneration, injected into the brains of ordinary mice, made the mice's own tau assemble into filaments with the same structures as the injected material. Tau is a protein that clumps inside nerve cells in Alzheimer's disease, the most common of more than 20 brain diseases defined by tau filaments; corticobasal degeneration is a far less common one.

Most neurodegenerative diseases are thought to spread the way prion diseases do, with a misfolded protein forcing its shape onto normal copies of itself. The authors describe one assumption behind that account as a pillar of the prion hypothesis that had not been demonstrated: that a strain keeps its structural identity when it is passed on. They also say the mouse is now a suitable model for studying how distinct tau shapes drive each disease's damage. The paper was published online in Nature on Sept. 30, 2026.

Sofia Lövestam, Michel Goedert and Sjors H. W. Scheres of the MRC Laboratory of Molecular Biology in Cambridge, UK, did the work with colleagues at the Tokyo Metropolitan Institute of Medical Science. The mice were wild type, carrying no added human tau gene, and their brains were examined 9 to 12 months after injection. In mice given Alzheimer's filaments, 83% of those recovered were paired helical filaments, the form found in Alzheimer's brains. In mice given corticobasal degeneration filaments, the structures matched the type I filaments found in that disease. Mouse and human tau sequences are identical in the core of these filaments, which, the authors say, suggests there may be no species barrier.

The pattern of damage tracked the disease the filaments came from. Alzheimer's filaments, the authors report, produced tau deposits confined to nerve cells, while corticobasal degeneration filaments also produced deposits in glial cells, the brain's supporting cells, including the plaque-like inclusions around astrocytes seen in people with that disease. Tau filaments in earlier genetically engineered mouse models had structures unlike those in human brains.