1. Plasma Glial Fibrillary Acidic Protein Levels Differ Along the Spectra of Amyloid Burden and Clinical Disease Stage.
- Author
-
Asken, Breton M, Elahi, Fanny M, La Joie, Renaud, Strom, Amelia, Staffaroni, Adam M, Lindbergh, Cutter A, Apple, Alexandra C, You, Michelle, Weiner-Light, Sophia, Brathaban, Nivetha, Fernandes, Nicole, Karydas, Anna, Wang, Paul, Rojas, Julio C, Boxer, Adam L, Miller, Bruce L, Rabinovici, Gil D, Kramer, Joel H, and Casaletto, Kaitlin B
- Subjects
BRAIN metabolism ,PROTEIN metabolism ,RESEARCH ,ALZHEIMER'S disease ,NERVE tissue proteins ,AMYLOIDOSIS ,CROSS-sectional method ,RESEARCH methodology ,CYTOSKELETAL proteins ,ETHYLENE glycols ,MEDICAL cooperation ,EVALUATION research ,AMINES ,COMPARATIVE studies ,RADIOPHARMACEUTICALS ,RESEARCH funding ,PEPTIDES ,THIAZOLES ,LONGITUDINAL method - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF