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We aimed to define the regional organisation, stage dependence and clinical relevance of tau-sensitive PET signal across the HD disease spectrum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifty-four participants (13 healthy controls, 9 premanifest mutation carriers and 32 manifest carriers) underwent 60-minute dynamic [\u00b9\u2078F]PI-2620 PET imaging. Tau-PET signal was quantified using distribution volume ratios (DVR) derived from reference-tissue kinetic modelling. Analyses combined region-of-interest and whole-brain mapping with threshold-based positivity profiling, modelling of cumulative genetic disease burden (CAP), and clinico-anatomical association analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tau-PET abnormalities showed a spatially ordered pattern dominated by subcortical involvement. The globus pallidus exhibited the strongest effect, with marked DVR increases and high positivity rates emerging in premanifest carriers and approaching saturation in manifest HD. Additional subcortical changes involved the putamen, whereas caudate DVR decreased in manifest disease. Cortical effects were more modest and selectively involved posterior associative regions. CAP modelling supported predominantly monotonic subcortical stage-related profiles, while limbic and cortical regions showed heterogeneous cross-sectional patterns. Clinico-anatomical analyses linked subcortical tau-PET signal with genetic burden and motor severity and limbic signal with psychiatric symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tau-sensitive PET signal represents a spatially ordered and stage-dependent feature of HD and identifies a reproducible pallidal signature linked to disease burden, supporting its potential as a biomarker for patient stratification and mechanistic monitoring in therapeutic studies targeting downstream pathological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT07503743.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08003-0","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:01:06Z","timestamp":1782698466000},"page":"7376-7390","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stage-dependent tau-PET signatures in Huntington\u2019s disease revealed by [\u00b9\u2078F]PI-2620"],"prefix":"10.1007","volume":"53","author":[{"given":"Saul","family":"Martinez-Horta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Perez-Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnau","family":"Puig-Davi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valle","family":"Camacho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Perez-Carasol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Franch-Marti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Olmedo-Saura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Fernandez-Leon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Flotats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme D.","family":"Kolinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Bullich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Perez-Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pagonabarraga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Kulisevsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"8003_CR1","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","volume":"369","author":"FO Walker","year":"2007","unstructured":"Walker FO. 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JPP reports a grant from Fondo de Investigaciones Sanitarias (FIS) from Instituto de Salud Carlos III (ISCIII). JK has received honoraria for advisory boards or lecturing from: Teva, Zambon, UCB, Bial, General Electric, Sanofi, and Roche, and reports grants from Fundaci\u00f3 la Marato de TV3, Fondo de Investigaciones Sanitarias (FIS) from Instituto de Salud Carlos III (ISCIII), and Fondo Europeo de Desarrollo Regional (FEDER). JP has served on advisory or speakers\u2019 boards, and received honoraria from: UCB, Zambon, AbbVie, Italfarmaco, Allergan, Ipsen, Bial and reports grants from Fundaci\u00f3 la Marato de TV3, Fondo de Investigaciones Sanitarias (FIS) and from Instituto de Salud Carlos III (ISCIII). The authors declare that there is no conflict of interest regarding the publication of this article.\u00a0GDK, SB and EPM are employees of Life Molecular Imaging GmbH.\u00a0The rest of authors declare that they have no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}