Synergistic effects of GFAP and Aβ42: Implications for white matter integrity and verbal memory across the cognitive spectrum.

Autor:	Bettcher BM; Department of Neurology, Behavioral Neurology Section, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Lopez Paniagua D; Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Wang Y; Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., McConnell BV; Department of Neurology, Behavioral Neurology Section, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Coughlan C; Department of Neurology, University of Colorado Alzheimer's & Cognition Center, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Carlisle TC; Department of Neurology, Behavioral Neurology Section, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Thaker AA; Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Department of Radiology, Denver Health, Denver, CO, USA., Lippitt W; Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Filley CM; Behavioral Neurology Section, Departments of Neurology and Psychiatry, University of Colorado Alzheimer's & Cognition Center, Marcus Institute for Brain Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Pelak VS; Department of Neurology, Behavioral Neurology Section, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Shapiro ALB; Section of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Heffernan KS; Department of Neurology, Behavioral Neurology Section, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Potter H; Department of Neurology, University of Colorado Alzheimer's & Cognition Center, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Solano A; Department of Neurology, University of Colorado Alzheimer's & Cognition Center, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Boyd J; Department of Neurology, Behavioral Neurology Section, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Carlson NE; Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jazyk:	angličtina
Zdroj:	Brain, behavior, & immunity - health [Brain Behav Immun Health] 2024 Aug 03; Vol. 40, pp. 100834. Date of Electronic Publication: 2024 Aug 03 (Print Publication: 2024).
DOI:	10.1016/j.bbih.2024.100834
Abstrakt:	Background: Plasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer's disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory. Methods: In a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-β42 (Aβ42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter. Results: In individuals in the low plasma amyloid-β42 (Aβ42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p  = 0.007), higher mean diffusivity (MD; p  < 0.001), higher radial diffusivity (RD; p  < 0.001), and higher axial diffusivity (DA; p  = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aβ42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance. Discussion: Higher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aβ42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aβ42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brianne Bettcher reports financial support was provided by 10.13039/100000049National Institute on Aging. Brianne M Bettcher reports a relationship with 10.13039/100000049National Institute on Aging that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 Published by Elsevier Inc.)
Databáze:	MEDLINE
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