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. 2020 Jun 30;12(1):e12039.
doi: 10.1002/dad2.12039. eCollection 2020.

Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study

Melissa E Petersen  1 , Fan Zhang  2 , Nicole Schupf  3   4   5   6   7 , Sharon J Krinsky-McHale  8 , James Hall  9 , Mark Mapstone  10 , Amrita Cheema  11 , Wayne Silverman  12 , Ira Lott  12 , Michael S Rafii  13 , Benjamin Handen  14 , William Klunk  14 , Elizabeth Head  15 , Brad Christian  16 , Tatiana Foroud  17 , Florence Lai  18 , H Diana Rosas  19 , Shahid Zaman  20   21 , Beau M Ances  22 , Mei-Cheng Wang  23 , Benjamin Tycko  24 , Joseph H Lee  3   4   5   6 , Sid O'Bryant  9 ; Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS)
Affiliations

Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study

Melissa E Petersen et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Previously generated serum and plasma proteomic profiles were examined among adults with Down syndrome (DS) to determine whether these profiles could discriminate those with mild cognitive impairment (MCI-DS) and Alzheimer's disease (DS-AD) from those cognitively stable (CS).

Methods: Data were analyzed on n = 305 (n = 225 CS; n = 44 MCI-DS; n = 36 DS-AD) enrolled in the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS).

Results: Distinguishing MCI-DS from CS, the serum profile produced an area under the curve (AUC) = 0.95 (sensitivity [SN] = 0.91; specificity [SP] = 0.99) and an AUC = 0.98 (SN = 0.96; SP = 0.97) for plasma when using an optimized cut-off score. Distinguishing DS-AD from CS, the serum profile produced an AUC = 0.93 (SN = 0.81; SP = 0.99) and an AUC = 0.95 (SN = 0.86; SP = 1.0) for plasma when using an optimized cut-off score. AUC remained unchanged to slightly improved when age and sex were included. Eotaxin3, interleukin (IL)-10, C-reactive protein, IL-18, serum amyloid A , and FABP3 correlated fractions at r2 > = 0.90.

Discussion: Proteomic profiles showed excellent detection accuracy for MCI-DS and DS-AD.

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Conflict of interest statement

SEO has patents and patents pending regarding blood‐biomarkers for precision medicine in neurodegenerative diseases and served on an Advisory Board to Roche Diagnostics. No other authors have conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Receiver operating characteristic (ROC) curves and variable importance plots for serum and plasma proteomic profile for detecting mild cognitive impairment‐Down syndrome (MCI‐DS). Note: MCI‐DS, fatty acid binding protein (FABP3), beta 2 microglobulin (B2M), pancreatic polypeptide (PPY), C‐reactive protein (CRP), soluble intercellular adhesion molecule‐1 (sICAM‐1), circulating vascular cell adhesion molecule‐1 (sVCAM‐1), tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐5, IL‐6, interleukin IL‐7, IL‐10, IL‐18, factor VII (Factor7), thymus and activation regulated chemokine (TARC), and serum amyloid A (SAA)
FIGURE 2
FIGURE 2
Receiver operating characteristic (ROC) curves and variable importance plots for serum and plasma proteomic profile for detecting Down syndrome‐Alzheimer's disease (DS‐AD). Note: fatty acid binding protein (FABP3), beta 2 microglobulin (B2M), pancreatic polypeptide (PPY), C‐reactive protein (CRP), soluble intercellular adhesion molecule‐1 (sICAM‐1), circulating vascular cell adhesion molecule‐1 (sVCAM‐1), tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐5, IL‐6, IL‐7, IL‐10, IL‐18, factor VII (Factor7), thymus and activation regulated chemokine (TARC), and serum amyloid A (SAA)
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References

    1. Rumble B, Retallack R, Hilbich C, et al. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease. N Engl J Med. 1989;320:1446‐1452. - PubMed
    1. Lott IT, Head E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol. 2019;15:135‐147. - PMC - PubMed
    1. Sabbagh M, Edgin J. Clinical assessment of cognitive decline in adults with Down syndrome. Curr Alzheimer Res. 2015;13:30‐34. - PubMed
    1. Schupf N, Patel B, Silverman W, et al. Elevated plasma amyloid β‐peptide 1‐42 and onset of dementia in adults with Down syndrome. Neurosci Lett. 2001;301:199‐203. - PubMed
    1. Schupf N, Patel B, Pang D, et al. Elevated plasma β‐amyloid peptide Aβ42 levels, incident dementia, and mortality in Down syndrome. Arch Neurol. 2007;64:1007‐1013. - PMC - PubMed