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Wagemann, O.* ; Nübling, G.* ; Martínez-Murcia, F.J.* ; Wlasich, E.* ; Loosli, S.V.* ; Sandkühler, K.* ; Stockbauer, A.* ; Prix, C.* ; Katzdobler, S.* ; Petrera, A. ; Hauck, S.M. ; Fortea, J.* ; Romero-Zaliz, R.* ; Jiménez-Mesa, C.* ; Górriz Sáez, J.M.* ; Höglinger, G.* ; Levin, J.*

Exploratory analysis of the proteomic profile in plasma in adults with Down syndrome in the context of Alzheimer's disease.

Alzheimers Dement. 21:e70040 (2025)

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INTRODUCTION: Adults with Down syndrome (DS) show increased risk for Alzheimer's disease (AD) due to the triplication of chromosome 21 encoding the amyloid precursor protein gene. Further, this triplication possibly contributes to dysregulation of the immune system, furthering AD pathophysiology. METHODS: Using Olink Explore 3072, we measured ∼3000 proteins in plasma from 73 adults with DS and 15 euploid, healthy controls (HC). Analyses for differentially expressed proteins (DEP) were carried out, and pathway and protein network enrichment using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING database was investigated. Within DS, the LASSO (least absolute shrinkage and selection operator) feature selection was applied. RESULTS: We identified 253 DEP between DS and HC and 142 DEP between symptomatic and asymptomatic DS. Several pathways regarding inflammatory and neurodevelopmental processes were dysregulated in both analyses. LASSO feature selection within DS returned 15 proteins as potential blood markers. DISCUSSION: This exploratory proteomic analysis found potential new blood biomarkers for diagnosing DS-AD in need of further investigation. HIGHLIGHTS: Inflammatory pathways are dysregulated in symptomatic versus asymptomatic DS. NFL and GFAP are confirmed as powerful biomarkers in DS with clinical and/or cognitive decline. Further circulating proteins were identified as potential blood biomarkers for symptomatic DS.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Alzheimer's Disease ; Down Syndrome ; Biomarker ; Neuroinflammation ; Plasma; Clinical-diagnosis; Biomarker Changes; Dementia; Protein; Neuroinflammation; Individuals; Impairment; Framework; Fetuses; Binding

ISSN (print) / ISBN 1552-5260

e-ISSN 1552-5279

Journal Alzheimer's & Dementia

Quellenangaben Volume: 21, Issue: 3, Article Number: e70040

Publisher Elsevier

Publishing Place New York, NY [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)

Grants Deutsche Forschungsgemeinschaft
Jerome Lejeune Foundation
VERUM Foundation
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas Program 1
Unión Europea
Una Manera de Hacer Europa