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

Breton M. Asken, Fanny M. Elahi, Renaud La Joie, Amelia Strom, Adam M. Staffaroni, Cutter A. Lindbergh, Alexandra C. Apple, Michelle You, Sophia Weiner-Light, Nivetha Brathaban, Nicole Fernandes, Anna Karydas, Paul Wang, Julio C. Rojas, Adam L. Boxer, Bruce L. Miller, Gil D. Rabinovici, Joel H. Kramer, Kaitlin B. Casaletto, Michelle Mielke

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Background: Measuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-ß (Aß) may shed light on astrocytic changes in aging and Alzheimer's disease (AD). Objective: To examine associations between plasma GFAP and cortical Aß 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 Aß-PET burden. Aß-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 Aß-PET positive, while clinically normal participants (CDR-SB=0) were a mix of Aß-PET positive and negative. Regression analyses evaluated main effect and interaction associations between plasma GFAP, Aß-PET, and clinical severity. Results: In both cohorts, plasma GFAP increased linearly with Aß-PET CLs in clinically normal older adults. In Cohort 2, which included participants with more severe clinical dysfunction and Aß-PET burden, the association between Aß and GFAP became curvilinear (inverted U-shape; quadratic model R2 change=0.165, p=0.009), and Aß-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 Aß-PET CLs and plasma GFAP, while older adults with dementia (CDR-SB>4.0) showed a strong, negative association of higher Aß-PET CLs with lower plasma GFAP. Conclusion: The relationship between astrocytic integrity and cortical Aß may be highly dynamic, with linear, positive associations early in disease that diverge in more severe disease stages.

Original languageEnglish
Pages (from-to)265-276
Number of pages12
JournalJournal of Alzheimer's Disease
Volume78
Issue number1
DOIs
StatePublished - 2020
Externally publishedYes

Keywords

  • Alzheimer's disease
  • amyloid
  • astrocyte
  • biomarker
  • glial fibrillary acidic protein
  • plasma

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