Imaging proteomics for diagnosis, monitoring and prediction of Alzheimer's disease

Neuroimage. 2014 Nov 15;102 Pt 2(Pt 2):657-65. doi: 10.1016/j.neuroimage.2014.08.041. Epub 2014 Aug 28.

Abstract

Proteomic and imaging markers have been widely studied as potential biomarkers for diagnosis, monitoring and prognosis of Alzheimer's disease. In this study, we used Alzheimer Disease Neuroimaging Initiative dataset and performed parallel independent component analysis on cross sectional and longitudinal proteomic and imaging data in order to identify the best proteomic model for diagnosis, monitoring and prediction of Alzheimer disease (AD). We used plasma proteins measurement and imaging data from AD and healthy controls (HC) at the baseline and 1 year follow-up. Group comparisons at baseline and changes over 1 year were calculated for proteomic and imaging data. The results were fed into parallel independent component analysis in order to identify proteins that were associated with structural brain changes cross sectionally and longitudinally. Regression model was used to find the best model that can discriminate AD from HC, monitor AD and to predict MCI converters from non-converters. We showed that five proteins are associated with structural brain changes in the brain. These proteins could discriminate AD from HC with 57% specificity and 89% sensitivity. Four proteins whose change over 1 year were associated with brain structural changes could discriminate AD from HC with sensitivity of 93%, and specificity of 92%. This model predicted MCI conversion to AD in 2 years with 94% accuracy. This model has the highest accuracy in prediction of MCI conversion to AD within the ADNI-1 dataset. This study shows that combination of selected plasma protein levels and MR imaging is a useful method in identifying potential biomarker.

Keywords: Alzheimer's disease; Biomarkers; Magnetic resonance imaging; Parallel ICA; Proteomics; Tensor based morphometry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology
  • Biomarkers
  • Brain / pathology*
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / diagnosis
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Male
  • Prognosis
  • Proteomics*

Substances

  • Biomarkers