NeuroMolecular Medicine

, Volume 18, Issue 4, pp 593–601

Plasma Amyloid Beta 1-42 and DNA Methylation Pattern Predict Accelerated Aging in Young Subjects with Down Syndrome

  • Rima Obeid
  • Ulrich Hübner
  • Marion Bodis
  • Juergen Geisel
Original Paper

DOI: 10.1007/s12017-016-8413-y

Cite this article as:
Obeid, R., Hübner, U., Bodis, M. et al. Neuromol Med (2016) 18: 593. doi:10.1007/s12017-016-8413-y

Abstract

Gene methylation is an age-related dynamic process that influences diseases. Premature aging and disturbed methylation are components of Down syndrome (DS). We studied blood biomarkers and DNA methylation (DNAm) of three CpG sites (ASPA, ITGA2B, and PDE4C) in 60 elderly subjects (mean age = 68 years), 31 subjects with DS (12.1 years) and 44 controls (12.8 years). Plasma concentrations of amyloid beta (Aβ) 1-42 and biomarkers of methylation were measured in the young groups. Subjects with DS had significantly higher concentrations of plasma S-adenosylhomocysteine (SAH) and Aβ and reduced S-adenosylmethionine/SAH ratio compared with the controls. Methylations (%) of ASPA and ITGA2B were lower in DS [mean difference; 95 % confidence intervals = −2.2 (−4.5, 0.1) for ASPA and −5.0 (−8.9, −1.1) for ITGA2B]. Methylation of PDE4C did not differ between the groups. The sum of z-scores for methylations of ASPA and ITGA2B, both of which declined with age, was significantly lower in DS [−1.01 (−1.93, −0.20), p = 0.017]. Subjects with DS were found to be 3.1 (1.5–4.6) years older than their predicted age based on a regression model of the controls. Elevated SAH levels predicted lower DNAm of ASPA and ITGA2B in stepwise regression analysis. Therefore, methylation of three CpGs combined with plasma Aβ has shown a 3-year accelerated aging in subjects with DS at the age of 12 years. Disorders in the methylation cycle explained pathoepigenetic modifications in subjects with DS. The influence of modifications in the methylation cycle on epigenetic markers of aging warrants further investigations.

Keywords

Trisomy 21 Amyloid beta DNA methylation Aging Epigenomics 

Abbreviations

Amyloid beta

APP

Amyloid precursor protein

DNAm

DNA methylation

DS

Down syndrome

Hcy

Homocysteine

SAH

S-adenosylhomocysteine

SAM

S-adenosylmethionine

Supplementary material

12017_2016_8413_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 kb)
12017_2016_8413_MOESM2_ESM.pptx (70 kb)
Supplementary material 2 (PPTX 69 kb)

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Rima Obeid
    • 1
    • 2
  • Ulrich Hübner
    • 1
  • Marion Bodis
    • 1
  • Juergen Geisel
    • 1
  1. 1.Department of Clinical Chemistry and Laboratory MedicineSaarland University HospitalHomburg/SaarGermany
  2. 2.Aarhus Institute of Advanced StudiesUniversity of AarhusAarhus CDenmark

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