Researchers at the Sant Pau Research Institute and Hospital de Sant Pau have detected, for the first time in living people, a tau-related brain pattern that shifts according to the stage of Huntington's disease. Using positron emission tomography with the second-generation radiotracer [18F]PI-2620, the team found the signal in some carriers of the Huntington's mutation who had not yet developed clinically evident disease, and showed that it grows stronger and spreads through the brain in an organized anatomical pattern as the disease advances.
The work, published in the European Journal of Nuclear Medicine and Molecular Imaging, addresses a long-standing gap between the genetic mutation that causes Huntington's and the motor, cognitive, and neuropsychiatric symptoms that eventually follow. Tau has been suspected of playing a role in the disease for some time, but as first author Dr. Saul Martinez-Horta, a neuropsychologist in the Movement Disorders Unit at Hospital de Sant Pau, points out, no one had been able to see how the signal was distributed or how it changed across disease stages in a living brain. His team reports that the process is already underway before manifest disease and follows a clearly defined anatomical organization, especially in certain subcortical regions.
The practical significance lies in measurement. Huntington's currently has no disease-modifying therapies, and any future treatment will need reliable markers to show whether it is working, ideally before irreversible damage accumulates. A tau signal that tracks with disease stage and appears in pre-symptomatic carriers could serve that monitoring role, and it also points to a potential target: the researchers suggest tau-related changes may be part of a cascade of secondary mechanisms that amplify or otherwise shape how the disease progresses.
That framing matters for the wider dementia field as well, since tau imaging has been developed largely in the context of Alzheimer's disease. Finding a stage-dependent tau pattern in a genetically defined condition like Huntington's gives researchers an unusually clean setting in which to study how tau pathology unfolds over time relative to a known trigger.