{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:35:54Z","timestamp":1789266954602,"version":"build-2803163510"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["Tifft ZIAHG200409"],"award-info":[{"award-number":["Tifft ZIAHG200409"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020940","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020940","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural History Protocol","award":["NCT00029965"],"award-info":[{"award-number":["NCT00029965"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>GM1 gangliosidosis is an ultra-rare inherited neurodegenerative lysosomal storage disorder caused by biallelic mutations in the GLB1 gene. GM1 is uniformly fatal and has no approved therapies, although clinical trials investigating gene therapy as a potential treatment for this condition are underway. Novel outcome measures or markers demonstrating the longitudinal effects of GM1 and potential recovery due to therapeutic intervention are urgently needed to establish efficacy of potential therapeutics. One promising tool is differential tractography, a novel imaging modality utilizing serial diffusion tensor imaging to quantify longitudinal changes in white matter microstructure. In this study, we present the novel use of differential tractography in quantifying the progression of GM1 alongside age-matched neurotypical controls. We analysed 113 diffusion tensor imaging scans from 16 GM1 patients and 32 age-matched neurotypical controls to investigate longitudinal changes in white matter pathology. GM1 patients showed white matter degradation evident by both the number and size of fibre tract loss. In contrast, neurotypical controls showed longitudinal white matter improvements as evident by both the number and size of fibre tract growth. We also corroborated these findings by documenting significant correlations between clinical global impression scores of clinical presentations and our differential tractography derived metrics in our GM1 cohort. Specifically, GM1 patients who lost more neuronal fibre tracts also had a worse clinical presentation. This result demonstrates the utility of differential tractography as a marker for disease progression in GM1 patients with potential extension to other neurodegenerative diseases and therapeutic intervention.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf198","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:42:07Z","timestamp":1747993327000},"source":"Crossref","is-referenced-by-count":5,"title":["Differential tractography: an imaging marker for tissue degeneration in neurodegenerative diseases"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8204-5848","authenticated-orcid":false,"given":"Connor J","family":"Lewis","sequence":"first","affiliation":[{"name":"Office of the Clinical Director, National Human Genome Research Institute , Bethesda, MD 20892 ,","place":["USA"]},{"name":"Medical Genetics Branch, National Human Genome Research Institute , Bethesda, MD 20892 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