Tiny amounts of human tau seeds from Alzheimer’s disease and corticobasal degeneration (CBD) triggered a chain reaction in healthy mouse brains, forcing the animals’ own tau to misfold into exact 3D copies of the diseased originals. The findings, published in Nature by Sofia Loevstam and colleagues, offer the most direct structural evidence yet for the prion hypothesis of tau spread.

Using high-resolution cryo-electron microscopy, researchers found that Alzheimer’s seeds made mouse tau adopt the exact Alzheimer’s fold, the paired helical filament, while CBD seeds produced the exact CBD fold. The human seeds vanished within a week, but the misfolding cascade continued for nine to 12 months.

The shape also decided which brain cells were hit: Alzheimer’s seeds produced clumps only inside nerve cells, while CBD seeds struck both neurons and supporting glial cells, matching the cell-loss patterns seen in patients. The researchers say the work could help test drugs that block tau seeding and lead to disease-specific diagnostic tools.