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This review discusses recent advances in fluid and neuroimaging biomarkers since the introduction of the HD-Integrated Staging System (HD-ISS), focusing on candidates with the most relevant evidence for regulatory applications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>Neurofilament light (NfL) has become a versatile biomarker for prognostic enrichment and safety monitoring. Mutant huntingtin (mHTT) and somatic expansion ratio (SER) provide mechanistic evidence of target engagement. HD-YAS showed SER predicts striatal atrophy over multi-year intervals, but its short-term sensitivity remains uncertain. Structural MRI remains the most sensitive imaging marker of progression, whilst PET and diffusion imaging offer mechanistic insight but limited temporal sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>The most advanced biomarkers now span neuronal injury, target engagement and neurodegeneration. Moving toward qualified endpoints will require harmonised methods, improved analytical validation and stronger evidence linking biomarker change to clinical benefit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11910-026-01522-1","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:59:07Z","timestamp":1790236747000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluid and Imaging Biomarkers in Huntington\u2019s Disease"],"prefix":"10.1007","volume":"26","author":[{"given":"Elizabeth L.","family":"Broom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Hanson-Baiden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"1522_CR1","doi-asserted-by":"publisher","unstructured":"Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, et al. 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Broom and Joelle Hanson-Baiden have no disclosures to report. Lauren M. Byrne reports grants from Rosetrees Trust (pilot grant: Seedcorn2023\\100196); consulting fees from Alchemab, LoQus23, PTC Therapeutics, and Latus Bio; support for attending meetings and\/or travel from CHDI Foundation, Huntington Study Group, and EHDN; Huntington\u2019s Disease Youth Organization (Board Member), Huntington\u2019s Disease Association N. I. (Board Member), EHDN Pediatric HD working group (Co-lead facilitator), and EHDN Fluid Biomarkers working group (Co-lead facilitator).","order":1,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":2,"name":"Ethics","label":"Human and Animal Rights and Informed Consent","group":{"name":"EthicsHeading","label":"Declaration"}}],"article-number":"51"}}