Exploratory analysis of the proteomic profile in plasma in adults with Down syndrome in the context of Alzheimer's disease
Wagemann, O. (German Center for Neurodegenerative Disease (DZNE))
Nübling, G. (Ludwig-Maximilians-University (LMU) Munich)
Martínez-Murcia, F.J. (Universidad de Granada)
Wlasich, E. (Ludwig-Maximilians-University (LMU) Munich)
Loosli, S.V. (University Hospital Zurich (Suïssa))
Sandkühler, K. (Ludwig-Maximilians-University (LMU) Munich)
Stockbauer, A. (German Center for Neurodegenerative Disease (DZNE))
Prix, C. (Ludwig-Maximilians-University (LMU) Munich)
Katzdobler, S. (German Center for Neurodegenerative Disease (DZNE))
Petrera, A. (German Research Center for Environmental Health (GmbH))
Hauck, S.M. (German Research Center for Environmental Health (GmbH))
Fortea, Juan (Institut de Recerca Sant Pau)
Romero-Zaliz, R. (Universidad de Granada)
Jiménez-Mesa, C. (Universidad de Granada)
Górriz Sáez, J.M. (Universidad de Granada)
Höglinger, G. (Munich Cluster for Systems Neurology (SyNergy))
Levin, J. (Munich Cluster for Systems Neurology (SyNergy))
Universitat Autònoma de Barcelona

Data:	2025
Resum:	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.
Ajuts:	Agencia Estatal de Investigación PID2022-137629OA-I00 European Commission H2020-SC1-BHC-2018-2020 Instituto de Salud Carlos III PI20/01473 Instituto de Salud Carlos III PI23/01786
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Down syndrome ; Biomarker ; Neuroinflammation ; Plasma
Publicat a:	Alzheimer's & dementia, Vol. 21 Núm. 3 (march 2025) , p. e70040, ISSN 1552-5279

DOI: 10.1002/alz.70040
PMID: 40110647

14 p, 1.8 MB

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