Evidence map›Paper›PMID 42679336›Full record

ArticleNeurology2026

Longitudinal Dynamics of the Blood Proteome Within the Alzheimer Spectrum in Down Syndrome.

Olivia Wagemann, Georg S Nuebling, Katja Sandkühler, Elisabeth Wlasich, Sandra V Loosli, Catharina Prix, Anna Christina Stockbauer, Lena Marth, Anabel Forte, Jonathan Vöglein and 6 more

Abstract read
In one paragraph

Article in Neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Olivia WagemannDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0000-0003-3211-9105
Georg S NueblingDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.
Katja SandkühlerDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0009-0000-7117-2270
Elisabeth WlasichDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0009-0002-2733-7511
Sandra V LoosliDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0000-0003-0667-1676
Catharina PrixDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0009-0007-5058-1586
Anna Christina StockbauerDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0009-0006-8944-5568
Lena MarthDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0009-0004-9980-9981
Anabel ForteDepartment of Statistics and I.O., University of Valencia, Burjassot, Spain.ORCID 0000-0001-9534-1817
Jonathan VögleinDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0000-0002-5965-838X
Sabrina KatzdoblerDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0000-0002-3512-5984
Alexander Maximilian BernhardtDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0000-0002-2572-5062
Francisco J Martinez-MurciaDepartment of Signal Theory, Telematics and Communications, Andalusian Institute in Data Science and Computational Intelligence (DaSCI) at University of Granada, Spain.ORCID 0000-0001-8146-7056
Carmen Jiménez-MesaDepartment of Communications Engineering, University of Málaga, Spain; and.
Günter U HöglingerDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0000-0001-7587-6187
Johannes LevinDepartment of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.ORCID 0000-0001-5092-4306

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesAdults with Down syndrome (DS) have an increased risk of developing early Alzheimer disease. While our previous cross-sectional study investigated the blood proteome in the context of Alzheimer in DS, identifying CBLN4, CD14, C-X-C motif chemokine 17 (CXCL17), ectodysplasin A2 receptor (EDA2R), glial fibrillary acidic protein (GFAP), insulin-like growth factor binding protein-2 (IGFBP2), neurofilament light (NFL), SEPTIN3, and SPON1 as proteins of interest, longitudinal trajectories remain mostly unexplored. We aimed to characterize the longitudinal dynamics of these plasma proteins to evaluate their potential contribution to disease pathophysiology and associated cognitive decline.

methodsAdults with diagnosis of DS and ability to understand instructions of neuropsychological assessments were recruited at Ludwig Maximilians University Hospital Munich, returning for at least 1 annual follow-up visit for repeated clinical assessment, neuropsychological testing, and blood sample collection after baseline visit. Longitudinal blood protein dynamics were assessed using OLINK technology. Bayesian modeling analyzed longitudinal protein trajectories and their impact on cognitive performance. Spearman correlations of regression-derived rates of change investigated relationships between proteins and cognitive subdomains stratified by clinical diagnosis.

resultsWe included 59 adults with DS (46% female, median age = 32 years [interquartile range: 27-47]). All completed the first annual follow-up visit (median duration 13.37 months [12.35-20.95]), with 14 of them returning for a follow-up 2 visit (median 25.43 months [24.79-33.8]). Stratified analysis included 13 individuals with DS with (38% female, 54 years [49-58]) and 41 without diagnosis of cognitive decline (49% female, 29 years [24-35]). Cluster of differentiation 14, CXCL17, EDA2R, GFAP, IGFBP2, NFL, SEPTIN3, and SPON1 exhibited longitudinal increase, while CBLN4 decreased (all posterior distributions ≥ 99.12%), with age. Protein baseline levels were associated with cognitive decline over time while controlling for age in the whole cohort (all posterior distributions ≥ 94.75%). After correction for multiple comparisons, no longitudinal changes in protein markers exhibited a significant relationship when correlated with changes in cognitive subdomain performance within subcohorts. DISCUSSION: In DS, longitudinal characterization of all previously identified proteins revealed distinct trajectories over time and an association of baseline levels with future cognitive decline. This suggests potential contributions of these proteins to the complex underlying pathophysiology of Alzheimer in DS and should motivate further investigation.

Indexed as

Alzheimer DiseaseDown SyndromeProteomeAdultBiomarkersCross-Sectional StudiesFemaleHumansLongitudinal StudiesMaleMiddle AgedNeuropsychological TestsBiomarkersProteome

Identifiers

PMID42679336
PMCPMC13552366

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