{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:38:08Z","timestamp":1776440288863,"version":"3.51.2"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01NS110100"],"award-info":[{"award-number":["R01NS110100"]}]},{"name":"NIH","award":["1S10OD026918-01A1"],"award-info":[{"award-number":["1S10OD026918-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fragile X-associated Tremor\/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder associated with the FMR1 premutation. Currently, it is not possible to determine when and if individual premutation carriers will develop FXTAS. Thus, with the aim to identify biomarkers for early diagnosis, development, and progression of FXTAS, along with associated dysregulated pathways, we performed blood proteomic profiling of premutation carriers (PM) who, as part of an ongoing longitudinal study, emerged into two distinct groups: those who developed symptoms of FXTAS (converters, CON) over time (at subsequent visits) and those who did not (non-converters, NCON). We compared these groups to age-matched healthy controls (HC). We assessed CGG repeat allele size by Southern blot and PCR analysis. The proteomic profile was obtained by liquid chromatography mass spectrometry (LC-MS\/MS). We identified several significantly differentiated proteins between HC and the PM groups at Visit 1 (V1), Visit 2 (V2), and between the visits. We further reported the dysregulated protein pathways, including sphingolipid and amino acid metabolism. Our findings are in agreement with previous studies showing that pathways involved in mitochondrial bioenergetics, as observed in other neurodegenerative disorders, are significantly altered and appear to contribute to the development of FXTAS. Lastly, we compared the blood proteome of the PM who developed FXTAS over time with the CSF proteome of the FXTAS patients recently reported and found eight significantly differentially expressed proteins in common. To our knowledge, this is the first report of longitudinal proteomic profiling and the identification of unique biomarkers and dysregulated protein pathways in FXTAS.<\/jats:p>","DOI":"10.3390\/ijms241713477","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:44:46Z","timestamp":1693388686000},"page":"13477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Blood Proteome Profiling Reveals Biomarkers and Pathway Alterations in Fragile X PM at Risk for Developing FXTAS"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-0535","authenticated-orcid":false,"given":"Marwa","family":"Zafarullah","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Genome Center, Bioinformatics Core, University of California Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle R.","family":"Salemi","sequence":"additional","affiliation":[{"name":"Genome Center, Proteomics Core, Genome and Biomedical Sciences Facility, University of California Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3870-3302","authenticated-orcid":false,"given":"Brett S.","family":"Phinney","sequence":"additional","affiliation":[{"name":"Genome Center, Proteomics Core, Genome and Biomedical Sciences Facility, University of California Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blythe P.","family":"Durbin-Johnson","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-8448","authenticated-orcid":false,"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[{"name":"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hessl","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-4774","authenticated-orcid":false,"given":"Susan M.","family":"Rivera","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Psychology, University of California Davis, Davis, CA 95616, USA"},{"name":"Department of Psychology, University of Maryland, College Park, MD 20742, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-9180","authenticated-orcid":false,"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cabal-Herrera, A.M., Tassanakijpanich, N., Salcedo-Arellano, M.J., and Hagerman, R.J. 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