Plasma Glial Fibrillary Acidic Protein Levels Differ Along the Spectra of Amyloid Burden and Clinical Disease Stage¹

Article type: Research Article

Authors: 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. | Casaletto, Kaitlin B.

Affiliations: Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California at San Francisco (UCSF), San Francisco, CA, USA

Correspondence: [*] Correspondence to: Breton Asken, PhD, ATC, Postdoctoral Fellow, University of California, San Francisco, Weill Institute for Neurosciences, Department of Neurology, Memory and Aging Center, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94158, USA. Tel.: +1 415 476 3722; E-mail: breton.asken@ucsf.edu.

Note: [1] This article received a correction notice (Erratum) with the reference: 10.3233/JAD-219001, available at https://content.iospress.com/articles/journal-of-alzheimers-disease/jad219001.

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.

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

DOI: 10.3233/JAD-200755

Journal: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 265-276, 2020