Tau buildup in progressive supranuclear palsy alters brain networks linked to thinking and behavior

Researchers at Japan's National Institutes for Quantum Science and Technology (QST) have found that tau buildup in progressive supranuclear palsy (PSP) may affect brain networks involved in thinking and behavior. 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.

PSP 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 PSP 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, the QST team combined tau positron emission tomography (tau PET) with brain network mapping. Using a tau PET tracer developed by QST, the researchers visualized tau deposits in 37 patients with PSP. They then combined each patient's tau-affected areas with brain connectivity data from 100 healthy individuals to identify distant regions that were functionally connected to the sites of pathology.