Identification of candidate serum protein biomarkers in Down's syndrome dementia

Topic: Amyloid, tau and blood-test diagnosis

MOLDI-MS identified eighty-five proteins represented by multiple tryptic peptides, twenty-five of which showed significant differences between DS and controls, confirmed by WB and ELISA analysis. Those differentially expressed proteins are amyloid b, afamin, a1-microglobulin, apolipoprotein C-II, apolipoprotein E, ABCG1, ceruloplasmin, complement (C1r, C1q), clusterin, cystatin-C, defensin, DPPIV/CD26, ferritin, hepcidin, histone, tau, themis, TREM2, transthyretin, serum amyloid P, myocardin-like protein 2, neuronal pentraxin receptor, retinol binding protein-4 (RBP4) and TGFb. CD26 expression patterns reduced in the DS brain, amyloid b and transthyretin, were significantly up-regulated, clusterin and retinol binding protein-4 were down-regulated in the DS serum. Statical analysis was evaluated by ANOVA (*** =p<0.001and **** =p<0.0001). Several of the differentially expressed proteins identified in this study have previously been linked as risk factors for Alzheimer disease and are components of functional pathways thought to contribute to the pathogenesis of AD and DSAD. These pathways include immune cell activation, reverse cholesterol transport, regulator of iron homeostasis and inhibition of Ab fibrils and oligomers. Furthermore, the significant difference of concentrations of these proteins in the sera of DS individuals may be further developed to generate non-invasive methods to identify and track the progression of AD, even in the prodromal phases.

@article{rahachowdhury2025-41449809,
  author  = {Raha‐Chowdhury, Ruma},
  title   = {{Identification of candidate serum protein biomarkers in Down's syndrome dementia}},
  journal = {Alzheimer s \& Dementia},
  year    = {2025},
  doi     = {10.1002/alz70856_102904},
  pmid    = {41449809},
  url     = {https://doi.org/10.1002/alz70856_102904}
}

Key findings

• MOLDI-MS identified eighty-five proteins represented by multiple tryptic peptides, twenty-five of which showed significant differences between DS and controls, confirmed by WB and ELISA analysis.
• Those differentially expressed proteins are amyloid b, afamin, a1-microglobulin, apolipoprotein C-II, apolipoprotein E, ABCG1, ceruloplasmin, complement (C1r, C1q), clusterin, cystatin-C, defensin, DPPIV/CD26, ferritin, hepcidin, histone, tau, themis, TREM2, transthyretin, serum amyloid P, myocardin-like protein 2, neuronal pentraxin receptor, retinol binding protein-4 (RBP4) and TGFb.
• CD26 expression patterns reduced in the DS brain, amyloid b and transthyretin, were significantly up-regulated, clusterin and retinol binding protein-4 were down-regulated in the DS serum.
• Statical analysis was evaluated by ANOVA (*** =p<0.001and **** =p<0.0001).
• Several of the differentially expressed proteins identified in this study have previously been linked as risk factors for Alzheimer disease and are components of functional pathways thought to contribute to the pathogenesis of AD and DSAD.

Why it matters

This study identified 25 serum proteins that differed significantly between people with Down syndrome and controls, some of which have been linked to Alzheimer disease risk pathways. The authors suggest these proteins may be developed into non-invasive markers, but no treatment, cure or prevention is tested.

Study details

• Participants50
• Evidence strengthLow

Read the original

• DOI: 10.1002/alz70856_102904
• PubMed: 41449809
• Original source →
• Free full text: Alzheimer s & Dementia →

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