Plasma Glial Fibrillary Acidic Protein Levels Differ Along the Spectra of Amyloid Burden and Clinical Disease Stage

J Alzheimers Dis. 2020;78(1):265-276. doi: 10.3233/JAD-200755.


Background: Measuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-β (Aβ) may shed light on astrocytic changes in aging and Alzheimer's disease (AD).

Objective: To examine associations between plasma GFAP and cortical Aβ deposition in older adults across the typical aging-to-AD dementia spectrum.

Methods: We studied two independent samples from UCSF (Cohort 1, N = 50; Cohort 2, N = 37) covering the spectra of clinical severity (CDR Sum of Boxes; CDR-SB) and Aβ-PET burden. Aβ-PET was completed with either florbetapir or Pittsburgh Compound B and standardized uptake value ratios were converted to the Centiloid (CL) scale for analyses. All participants with CDR-SB > 0 were Aβ-PET positive, while clinically normal participants (CDR-SB = 0) were a mix of Aβ-PET positive and negative. Regression analyses evaluated main effect and interaction associations between plasma GFAP, Aβ-PET, and clinical severity.

Results: In both cohorts, plasma GFAP increased linearly with Aβ-PET CLs in clinically normal older adults. In Cohort 2, which included participants with more severe clinical dysfunction and Aβ-PET burden, the association between Aβ and GFAP became curvilinear (inverted U-shape; quadratic model R2 change = 0.165, p = 0.009), and Aβ-PET interacted with CDR-SB (R2 change = 0.164, p = 0.007): older adults with intermediate functional impairment (CDR-SB = 0.5-4.0) showed a weak (negative) association between Aβ-PET CLs and plasma GFAP, while older adults with dementia (CDR-SB > 4.0) showed a strong, negative association of higher Aβ-PET CLs with lower plasma GFAP.

Conclusion: The relationship between astrocytic integrity and cortical Aβ may be highly dynamic, with linear, positive associations early in disease that diverge in more severe disease stages.

Keywords: Alzheimer’s disease; amyloid; astrocyte; biomarker; glial fibrillary acidic protein; plasma.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Amyloidogenic Proteins / metabolism
  • Amyloidosis / metabolism
  • Aniline Compounds
  • Brain / metabolism
  • Cognitive Dysfunction / metabolism
  • Cohort Studies
  • Cross-Sectional Studies
  • Ethylene Glycols
  • Female
  • Glial Fibrillary Acidic Protein / blood*
  • Humans
  • Male
  • Positron-Emission Tomography
  • Radiopharmaceuticals / metabolism
  • Thiazoles
  • tau Proteins / metabolism


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • Aniline Compounds
  • Ethylene Glycols
  • Glial Fibrillary Acidic Protein
  • Radiopharmaceuticals
  • Thiazoles
  • tau Proteins
  • florbetapir