Inflammatory biomarkers in Alzheimer's disease plasma

Alzheimers Dement. 2019 Jun;15(6):776-787. doi: 10.1016/j.jalz.2019.03.007. Epub 2019 Apr 30.

Abstract

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers.

Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.

Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).

Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.

Keywords: Alzheimer's disease; Biomarker; Complement; Inflammation; Plasma.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Amyloid beta-Peptides / blood
  • Biomarkers / blood*
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / diagnosis
  • Cohort Studies
  • Complement Factor B
  • Complement Factor H
  • Humans
  • Inflammation*
  • Internationality
  • Prognosis

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Complement Factor H
  • Complement Factor B