Researchers at Japan's National Institutes for Quantum Science and Technology have found that tau buildup in progressive supranuclear palsy may affect brain networks involved in thinking and behavior, according to a July 17 announcement. The findings suggest that symptoms may arise not only from where tau builds up in the brain, but also from how those affected areas are connected to distant brain regions.
The study was published online on July 10 in Science Advances. Progressive supranuclear palsy is a rare neurodegenerative disease caused by the abnormal accumulation of tau, a protein associated with several forms of dementia. The disease often leads to falls, problems with eye movement, stiffness, and cognitive or behavioral symptoms such as reduced attention and difficulty controlling emotions.
A long-standing question in progressive supranuclear palsy is why patients develop cognitive symptoms even when tau is concentrated mainly in deep brain regions involved in movement. Many of the symptoms appear to involve the cerebral cortex—the outer layer of the brain that supports attention, decision-making, and flexible behavior—even when those cortical areas show little direct tau buildup.
To investigate this mismatch, researchers combined tau positron emission tomography with brain network mapping. Using a tracer developed by their institute, they visualized tau deposits in 37 patients with progressive supranuclear palsy. Each patient's tau-affected areas were then combined with connectivity data from 100 healthy individuals to identify distant regions functionally connected to sites of pathology.
Although locations of tau buildup differed among patients, affected regions were commonly connected to a shared set of cortical areas—including the prefrontal cortex, anterior cingulate cortex, anterior insula, and parietal cortex—regions involved in executive functions such as attention and behavioral control. The strength of connection between each patient's tau deposits and this network was associated with severity of frontal cognitive impairment. In contrast, the amount of tau in deep brain regions was associated with motor symptoms but not cognitive ones.
"These results suggest that we should not view neurodegenerative disease only as damage at isolated spots in the brain," Dr. Hirabayashi said. "By identifying the circuits that connect pathology to symptoms, we hope to contribute to treatments that are better matched to each patient's condition."
