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Blood proteome profiling reveals biomarkers and pathway al-terations in fragile X PM at risk for developing fragile X

ABSTRACT: Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder associ-ated with the FMR1 premutation. Currently, it is not possible to determine when, and if, individ-ual premutation carriers will develop FXTAS. Thus, with the aim to identify biomarkers for early diagnosis, development, and progression of FXTAS, along with associated dysregulated path-ways, 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) overtime (at subsequent visits) and those who did not (non-converters, NCON). We compared these groups to age-matched healthy controls (HC). We assessed CGG re-peat 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 differenti-ated 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 in-volved 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 identification of unique biomarkers and dysregulated protein pathways of FXTAS

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Flora Tassone

PROVIDER: MSV000092680 | MassIVE | Thu Aug 17 08:00:00 BST 2023

SECONDARY ACCESSION(S): PXD044608

REPOSITORIES: MassIVE

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Blood proteome profiling reveals biomarkers and pathway al-terations in fragile X PM at risk for developing fragile X

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