The Correlation between Inflammatory Biomarkers and Polygenic Risk Score in Alzheimer's Disease

J Alzheimers Dis. 2017;56(1):25-36. doi: 10.3233/JAD-160889.


Plasma biomarkers to aid the early diagnosis of Alzheimer's disease (AD) or to monitor disease progression have long been sought and continue to be widely studied. Biomarkers that correlate with AD polygenic risk score, a measure of the polygenic architecture of the disease and highly predictive of AD status, would be excellent candidates. Therefore, we undertook a preliminary study to assess the association of plasma inflammatory biomarkers with an overall AD polygenic risk score as well as with an inflammation-specific AD polygenic risk score in a sample set of 93 AD cases. We measured five complement biomarkers [complement receptor 1 (CR1), clusterin, complement component 9 (C9), C1 inhibitor (C1inh), terminal complement complex (TCC)] and the benchmark inflammatory marker C-reactive protein (CRP). Plasma clusterin level showed an association with overall AD polygenic risk score, while clusterin, C1inh, and CRP levels each displayed some association with the inflammatory-specific AD polygenic risk score. The results suggest that elevated plasma levels of inflammatory biomarkers, including complement proteins, associate with polygenic risk scores in AD, further strengthening the link between genetic and biomarker disease predictors and indicating a potential role for these markers in disease prediction and patient stratification in AD.

Keywords: Alzheimer’s disease; biomarker; complement; inflammation; polygenic risk score.

Publication types

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

MeSH terms

  • Alzheimer Disease / blood*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism
  • Clusterin / blood
  • Complement C1 Inhibitor Protein / metabolism
  • Cytokines / blood*
  • Disease Progression
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / etiology*
  • Male
  • Multifactorial Inheritance / genetics
  • Neuropsychological Tests
  • Receptors, Complement / blood
  • Risk Factors
  • Statistics as Topic
  • Statistics, Nonparametric


  • Biomarkers
  • CLU protein, human
  • Clusterin
  • Complement C1 Inhibitor Protein
  • Cytokines
  • Receptors, Complement
  • C-Reactive Protein