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

Wagemann, Olivia ; Nübling, Georg; Martínez‐Murcia, Francisco Jesús; Wlasich, Elisabeth; Loosli, Sandra V.; Sandkühler, Katja; Stockbauer, Anna; Prix, Catharina; Katzdobler, Sabrina ; Petrera, Agnese; Hauck, Stefanie M. ; Fortea, Juan; Romero‐Zaliz, Rocío; Jiménez‐Mesa, Carmen; Górriz Sáez, Juan M.; Höglinger, Günter und Levin, Johannes (2025): Exploratory analysis of the proteomic profile in plasma in adults with Down syndrome in the context of Alzheimer's disease. In: Alzheimer's & Dementia, Vol. 21, No. 3, e70040

Abstract

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.

• Item Type: Journal article
• Faculties: Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1552-5260
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198