Blood amyloid beta levels in healthy, mild cognitive impairment and Alzheimer's disease individuals: replication of diastolic blood pressure correlations and analysis of critical covariates

PLoS One. 2013 Nov 27;8(11):e81334. doi: 10.1371/journal.pone.0081334. eCollection 2013.

Abstract

Plasma amyloid beta (Aβ) levels are being investigated as potential biomarkers for Alzheimer's disease. In AB128 cross-sectional study, a number of medical relevant correlates of blood Aβ40 or Aβ42 were analyzed in 140 subjects (51 Alzheimer's disease patients, 53 healthy controls and 36 individuals diagnosed with mild cognitive impairment). We determined the association between multiple variables with Aβ40 and Aβ42 levels measured in three different blood compartments called i) Aβ directly accessible (DA) in the plasma, ii) Aβ recovered from the plasma matrix (RP) after diluting the plasma sample in a formulated buffer, and iii) associated with the remaining cellular pellet (CP). We confirmed that diastolic blood pressure (DBP) is consistently correlated with blood DA Aβ40 levels (r=-0.19, P=0.032). These results were consistent in the three phenotypic groups studied. Importantly, the observation resisted covariation with age, gender or creatinine levels. Observed effect size and direction of Aβ40 levels/DBP correlation are in accordance with previous reports. Of note, DA Aβ40 and the RP Aβ40 were also strongly associated with creatinine levels (r=0.599, P<<0.001) and to a lesser extent to urea, age, hematocrit, uric acid and homocysteine (p<0.001). DBP and the rest of statistical significant correlates identified should be considered as potential confounder factors in studies investigating blood Aβ levels as potential AD biomarker. Remarkably, the factors affecting Aβ levels in plasma (DA, RP) and blood cell compartments (CP) seem completely different.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / blood*
  • Analysis of Variance
  • Blood Chemical Analysis / methods*
  • Blood Pressure*
  • Case-Control Studies
  • Cognitive Dysfunction / blood*
  • Cognitive Dysfunction / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Regression Analysis
  • Reproducibility of Results

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)

Grant support

This work has been funded by Araclon Biotech Ltd., Fundació ACE, and is also supported by the Spanish Ministry of Health from Instituto de Salud Carlos III (Madrid) (FISS PI10/00954) and by Agència d’Avaluació de Tecnologia i Recerca Mèdiques. Departament de Salut de la Generalitat de Catalunya (grant num. 390). The funder, Araclon Biotech Ltd., had a role in study design and data collection, but had no role on analysis, decision to publish, or preparation of the manuscript. The rest of funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.