Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

Alzheimers Res Ther. 2021 Mar 27;13(1):68. doi: 10.1186/s13195-021-00804-9.


Introduction: Plasma glial fibrillary acidic protein (GFAP) is a marker of astroglial activation and astrocytosis. We assessed the ability of plasma GFAP to detect Alzheimer's disease (AD) pathology in the form of AD-related amyloid-β (Aβ) pathology and conversion to AD dementia in a mild cognitive impairment (MCI) cohort.

Method: One hundred sixty MCI patients were followed for 4.7 years (average). AD pathology was defined using cerebrospinal fluid (CSF) Aβ42/40 and Aβ42/total tau (T-tau). Plasma GFAP was measured at baseline and follow-up using Simoa technology.

Results: Baseline plasma GFAP could detect abnormal CSF Aβ42/40 and CSF Aβ42/T-tau with an AUC of 0.79 (95% CI 0.72-0.86) and 0.80 (95% CI 0.72-0.86), respectively. When also including APOE ε4 status as a predictor, the accuracy of the model to detect abnormal CSF Aβ42/40 status improved (AUC = 0.86, p = 0.02). Plasma GFAP predicted subsequent conversion to AD dementia with an AUC of 0.84 (95% CI 0.77-0.91), which was not significantly improved when adding APOE ε4 or age as predictors to the model. Longitudinal GFAP slopes for Aβ-positive and MCI who progressed to dementia (AD or other) were significantly steeper than those for Aβ-negative (p = 0.007) and stable MCI (p < 0.0001), respectively.

Conclusion: Plasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia.

Keywords: Alzheimer’s disease; Blood biomarkers; GFAP; Mild cognitive impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / genetics
  • Amyloid beta-Peptides
  • Biomarkers
  • Cognitive Dysfunction* / diagnosis
  • Glial Fibrillary Acidic Protein / blood*
  • Glial Fibrillary Acidic Protein / metabolism*
  • Humans
  • Peptide Fragments
  • tau Proteins


  • Amyloid beta-Peptides
  • Biomarkers
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • Peptide Fragments
  • tau Proteins