Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort

J Alzheimers Dis. 2020;74(1):213-225. doi: 10.3233/JAD-190434.


We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.

Keywords: Alzheimer’s disease; amyloid-β; biomarkers; plasma; proteomics.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnostic imaging
  • Apolipoprotein E4 / genetics
  • Biomarkers / blood*
  • Blood Proteins / analysis*
  • Body Burden
  • Cerebral Amyloid Angiopathy / blood*
  • Cerebral Amyloid Angiopathy / diagnostic imaging
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / diagnostic imaging
  • Cohort Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Proteomics*
  • ROC Curve
  • tau Proteins / cerebrospinal fluid


  • Apolipoprotein E4
  • Biomarkers
  • Blood Proteins
  • MAPT protein, human
  • tau Proteins