Exploratory analysis of the proteomic profile in plasma in adults with Down syndrome in the context of Alzheimer's disease
Alzheimer's & Dementia, 2025
Wagemann O., Nübling G., Martínez‐Murcia F., Wlasich E., Loosli S., Sandkühler K., Stockbauer A., Prix C., Katzdobler S., Petrera A., Hauck S., Fortea J., Romero‐Zaliz R., Jiménez‐Mesa C., Górriz Sáez J., Höglinger G., Levin J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology Other Diseases & Syndromes | Pathophysiology Patient Stratification | Plasma |  Olink Explore 3072/384 |
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.
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.