For the first time, scientists have produced evidence in living humans that the protein tau, which mars the brain in Alzheimer’s disease, spreads from neuron to neuron. Tau deposits are found inside neurons, where they are thought to inhibit or kill them, whereas β-amyloid forms plaques outside brain cells.
Researchers at the University of Cambridge in the United Kingdom combined two brain imaging techniques, functional magnetic resonance imaging and positron emission tomography scanning, in 17 Alzheimer’s patients to map both the buildup of tau and their brains’ functional connectivity-that is, how spatially separated brain regions communicate with each other.
Strikingly, they found the largest concentrations of the damaging tau protein in brain regions heavily wired to others, suggesting that tau may spread in a way analogous to influenza during an epidemic, when people with the most social contacts will be at greatest risk of catching the disease.
Nathan Spreng, a neuroscientist who studies brain networks and Alzheimer’s disease at the Montreal Neurological Institute and Hospital in Canada, calls the evidence for an infectionlike spread of tau “Fascinating and compelling.” But others note that the study did not follow patients across time, a big weakness that makes it difficult to conclude that “Tau spreading” caused the decreased functional connectivity, says Jorge Sepulcre of Harvard Medical School in Boston, who uses PET scanning to probe the impacts of neurodegenerative diseases on brain network connectivity.
Although he’s confident his team has already demonstrated the transneuronal spread of tau, Cope says that the Cambridge group is now following larger numbers of subjects with Alzheimer’s and tracking individuals across time with brain imaging.
The spread of tau could have implications for clinical care, he adds, if drugs can be developed that attack tau in synapses, outside of cells, locking it up inside affected cells early, before it can spread..