{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:47:36Z","timestamp":1783111656235,"version":"3.54.6"},"reference-count":94,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD 036071"],"award-info":[{"award-number":["HD 036071"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MIND Institute Intellectual and Developmental Disabilities Research Center","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fragile X-associated tremor\/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting subjects (premutation carriers) with a 55-200 CGG-trinucleotide expansion in the 5\u2032UTR of the fragile X mental retardation 1 gene (FMR1) typically after age 50. As both the presence of white matter hyperintensities (WMHs) and atrophied gray matter on magnetic resonance imaging (MRI) are linked to age-dependent decline in cognition, here we tested whether MRI outcomes (WMH volume (WMHV) and brain volume) were correlated with mitochondrial bioenergetics from peripheral blood monocytic cells in 87 carriers with and without FXTAS. As a parameter assessing cumulative damage, WMHV was correlated to both FXTAS stages and age, and brain volume discriminated between carriers and non-carriers. Similarly, mitochondrial mass and ATP production showed an age-dependent decline across all participants, but in contrast to WMHV, only FADH2-linked ATP production was significantly reduced in carriers vs. non-carriers. In carriers, WMHV negatively correlated with ATP production sustained by glucose-glutamine and FADH2-linked substrates, whereas brain volume was positively associated with the latter and mitochondrial mass. The observed correlations between peripheral mitochondrial bioenergetics and MRI findings\u2014and the lack of correlations with FXTAS diagnosis\/stages\u2014may stem from early brain bioenergetic deficits even before overt FXTAS symptoms and\/or imaging findings.<\/jats:p>","DOI":"10.3390\/ijms22179171","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:19:26Z","timestamp":1629937166000},"page":"9171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Brain Atrophy and White Matter Damage Linked to Peripheral Bioenergetic Deficits in the Neurodegenerative Disease FXTAS"],"prefix":"10.3390","volume":"22","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Mind and Brain, University of California Davis, Davis, CA 95618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-4242","authenticated-orcid":false,"given":"Eleonora","family":"Napoli","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[{"name":"The MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Public Health Sciences, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingratana","family":"McLennan","sequence":"additional","affiliation":[{"name":"The MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-8448","authenticated-orcid":false,"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[{"name":"The MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1033-7435","authenticated-orcid":false,"given":"Cecilia","family":"Giulivi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA"},{"name":"The MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.exger.2017.01.027","article-title":"Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases","volume":"94","author":"Bickford","year":"2017","journal-title":"Exp. 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