Brain‐peripheral proteome crosstalk in Alzheimer's disease with and without diabetes mellitus
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Le résumé fourni par la source
BACKGROUND: Although considerable research has investigated diabetes mellitus (DM) as a risk factor for Alzheimer's disease (AD) dementia, the mechanistic understanding of the associations between peripheral and central biological processes in AD and AD within DM remains limited. METHODS: We performed tandem mass tag-based phosphoproteome profiling on postmortem prefrontal cortex (n = 191), deltoid muscle (n = 191), and antemortem serum (n = 96) from older adults with/without pathologic AD and with/without DM (DM/NDM). RESULTS: We observed significant brain-muscle and brain-serum correlations in phosphorylated and unphosphorylated peptides. Among individuals with DM, 59 were with AD and 36 were without. Among NDM, 63 were with AD and 33 were without. In a differential expression analysis, muscle phosphorylated seryl-tRNA synthetase 2 (SARS2)-S126 was significantly expressed in pathologic AD, whereas relative abundance of serum alpha-2-HS-glycoprotein (AHSG)-S346 and insulin-like growth factor binding protein 2 (IGFBP2)-S142 showed marginal expression for AD within the DM strata. CONCLUSIONS: Elucidating central and peripheral proteome crosstalk is valuable for uncovering potential AD biomarkers in accessible (peripheral) biospecimens. HIGHLIGHTS: We profiled peptides in brain, muscle, and serum biosamples. The study design allowed discovery of diabetes-associated peptides in Alzheimer's disease (AD). Strong brain-muscle, but weaker brain-serum peptide correlations were identified. Muscle seryl-tRNA synthetase 2-S126 was linked to AD pathology. Serum insulin-like growth factor binding protein 2-S142 and alpha-2-HS-glycoprotein-S346 were linked to AD in persons with diabetes.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Brain‐peripheral proteome crosstalk in Alzheimer's disease with and without diabetes mellitus
- Date Crossref
- 01/01/2026
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Harvard University pays non établi dans la noticeUniversité ou école supérieure
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Rush University Medical Center pays non établi dans la noticeÉtablissement de santé
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Massachusetts General Hospital pays non établi dans la noticeÉtablissement de santé
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Pacific Northwest National Laboratory pays non établi dans la noticeStructure de recherche
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Cancer Research And Biostatistics pays non établi dans la noticeOrganisation à but non lucratif
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Department of Epidemiology Harvard T H Chan School of Public Health Boston Massachusetts USA pays non établi dans la noticeUniversité ou école supérieure
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Alzheimer's Clinical and Translational Research Unit pays non établi dans la noticeStructure de recherche
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Department of Biostatistics Harvard T H Chan School of Public Health Boston Massachusetts USA pays non établi dans la noticeUniversité ou école supérieure
Harvard University, Rush University Medical Center et Massachusetts General Hospital, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.