{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:03:53Z","timestamp":1778767433213,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke (NINDS)","doi-asserted-by":"publisher","award":["R01 1NS107131"],"award-info":[{"award-number":["R01 1NS107131"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke (NINDS)","doi-asserted-by":"publisher","award":["R01 HD036071"],"award-info":[{"award-number":["R01 HD036071"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development (NICHD)","doi-asserted-by":"publisher","award":["R01 1NS107131"],"award-info":[{"award-number":["R01 1NS107131"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development (NICHD)","doi-asserted-by":"publisher","award":["R01 HD036071"],"award-info":[{"award-number":["R01 HD036071"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shriners Hospitals","award":["R01 1NS107131"],"award-info":[{"award-number":["R01 1NS107131"]}]},{"name":"Shriners Hospitals","award":["R01 HD036071"],"award-info":[{"award-number":["R01 HD036071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Brain changes at the end-stage of fragile X-associated tremor\/ataxia syndrome (FXTAS) are largely unknown due to mobility impairment. We conducted a postmortem MRI study of FXTAS to quantify cerebrovascular disease, brain atrophy and iron content, and examined their relationships using principal component analysis (PCA). Intracranial hemorrhage (ICH) was observed in 4\/17 FXTAS cases, among which one was confirmed by histologic staining. Compared with seven control brains, FXTAS cases showed higher ratings of T2-hyperintensities (indicating cerebral small vessel disease) in the cerebellum, globus pallidus and frontoparietal white matter, and significant atrophy in the cerebellar white matter, red nucleus and dentate nucleus. PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus and amygdala, that were independent from a highly correlated number of regions with ICH and iron content in subcortical nuclei. Post-hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus and amygdala in FXTAS cases compared to controls, after adjusting for T2-hyperintensity ratings. These findings indicate that both ischemic and hemorrhagic brain damage may occur in FXTAS, with the former being marked by demyelination\/iron depletion and atrophy, and the latter by ICH and iron accumulation in basal ganglia.<\/jats:p>","DOI":"10.3390\/cells12141898","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T01:52:35Z","timestamp":1689904355000},"page":"1898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Postmortem MRI Study of Cerebrovascular Disease and Iron Content at End-Stage of Fragile X-Associated Tremor\/Ataxia Syndrome"],"prefix":"10.3390","volume":"12","author":[{"given":"Jun Yi","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Mind and Brain, University of California Davis, Davis, CA 95618, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard J.","family":"Sonico","sequence":"additional","affiliation":[{"name":"Imaging Research Center, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2412-9146","authenticated-orcid":false,"given":"Maria Jimena","family":"Salcedo-Arellano","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Health, Sacramento, CA 95817, USA"},{"name":"Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-8448","authenticated-orcid":false,"given":"Randi J.","family":"Hagerman","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California Davis Health, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Martinez-Cerdeno","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Health, Sacramento, CA 95817, USA"},{"name":"Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13100-020-00206-y","article-title":"Finding and extending ancient simple sequence repeat-derived regions in the human genome","volume":"11","author":"Shortt","year":"2020","journal-title":"Mob. 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