Chiba, Japan — 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 behaviour. 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, 2026, in Science Advances .
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.
Although the precise locations of tau buildup differed from patient to patient, the affected regions were commonly connected to a shared set of cortical areas. These included the prefrontal cortex, anterior cingulate cortex, anterior insula, and parietal cortex—regions involved in executive functions such as attention, planning, inhibition, and behavioral control. The researchers call this shared circuit the “PSP-tau network.”
The strength of the connection between each patient’s tau deposits and this PSP-tau network was associated with the severity of frontal cognitive impairment. In contrast, the amount of tau in deep brain regions was associated with motor symptoms, such as eye movement problems, but not with the same cognitive symptoms. The findings suggest that movement and cognitive symptoms in PSP may arise through different mechanisms: local tau-related damage in motor-related regions and remote disruption of a broader cognitive network.
“Our study began with a clinical question that could not be answered by looking only at where tau accumulates,” said Dr. Toshiyuki Hirabayashi, Senior Principal Researcher at the Advanced Neuroimaging Center, QST. “We wanted to know whether local tau pathology could affect distant brain regions through neural circuits and whether that remote effect could explain the symptoms patients experience.”
The results provide evidence that tau pathology in PSP can be linked to cognitive symptoms through a common remote brain network, even when the visible pattern of tau accumulation varies among patients. This circuit-based view may help explain why people with different patterns of brain pathology can develop similar symptoms.
The findings may also have implications beyond PSP. Tau buildup is a key feature of several neurodegenerative diseases, including Alzheimer’s disease. If disease-related proteins can impair cognition by disrupting connected brain circuits, similar approaches could help identify symptom-related networks in other disorders and support more accurate prediction of disease-related changes.
“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.”
In the longer term, this network-based view could help researchers better understand how tau-related diseases affect the brain and may support future efforts toward earlier diagnosis, more accurate symptom prediction, and more personalized treatment strategies.
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Reference
DOI: 10.1126/sciadv.aed0348
About National Institutes for Quantum Science and Technology, Japan
The National Institutes for Quantum Science and Technology (QST) was established in April 2016 to promote quantum science and technology in a comprehensive and integrated manner. The new organization was formed from the merger of the National Institute of Radiological Sciences (NIRS) with certain operations that were previously undertaken by the Japan Atomic Energy Agency (JAEA).
QST is committed to advancing quantum science and technology, creating world-leading research and development platforms, and exploring new fields, thereby achieving significant academic, social, and economic impacts.
About Dr. Toshiyuki Hirabayashi
Dr. Toshiyuki Hirabayashi is a Principal Investigator at the Advanced Neuroimaging Center, National Institutes for Quantum Science and Technology (QST), Japan. His research focuses on the neural mechanisms of brain networks and neurodegenerative diseases. His work has been published in high-impact journals such as Science, Neuron, Nature Commun., Trends in Neurosci., and Science Adv. His research spans a broad spectrum, from multi-scale chemogenetics in non-human primates to large-scale network analysis of neurodegenerative diseases. By bridging basic neuroscience and clinical neuroimaging, his work provides critical insights into how localized brain lesions impact global neural circuits and cognitive function.
Funding information
This work was supported by AMED under Grant Numbers JP25wm0625307 and JP25wm0625001, JST under Grant Number JPMJMS2024, and JSPS KAKENHI under Grant Numbers JP24H00734, JP25H01767, and JP23K11796.
Science Advances
Imaging analysis
People
Remote Network for Cognitive Symptoms Derived from Tau Accumulation in Progressive Supranuclear Palsy
10-Jul-2026
H.S. and M.H. hold patents on compounds related to this report. The current patent status includes one granted Japanese patent and multiple international applications derived from the same PCT filing. The name of the organization filing the patent: National Institutes for Quantum Science and Technology (QST). Filing date: 21 December 2012, Japanese registration date: 29 November 2013, Japanese issue date: 19 February 2014, WO publication date: 26 June 2014. Serial numbers: PCT/JP2012/083286, WO2014/097474, JP Patent No. 5422782, EP 12 884 742.3, CA 2894994, and HK 1208672. M.H. holds equity in APRINOIA Therapeutics. H.Shim. received lecture fees from Eisai Co., Ltd. and Eli Lilly and Company. H.Shim. also received research funding and participated in joint research with Splink Inc. All other authors declare they have no competing interests.