학술논문
Astrocyte biomarker signatures of amyloid-beta and tau pathologies in Alzheimer's disease
Document Type
Author
Ferrari-Souza, J. P.; Ferreira, P. C. L.; Bellaver, B.; Tissot, C.; Wang, Y. T.; Leffa, D. T.; Brum, Wagner S.; Lessa Benedet, Andréa; Ashton, Nicholas J.; De Bastiani, M. A.; Rocha, A.; Therriault, J.; Lussier, F. Z.; Chamoun, M.; Servaes, S.; Bezgin, G.; Kang, M. S.; Stevenson, J.; Rahmouni, N.; Pallen, V.; Poltronetti, N. M.; Klunk, W. E.; Tudorascu, D. L.; Cohen, A. D.; Villemagne, V. L.; Gauthier, S.; Blennow, Kaj, 1958; Zetterberg, Henrik, 1973; Souza, D. O.; Karikari, Thomas; Zimmer, E. R.; Rosa-Neto, P.; Pascoal, T. A.
Source
Molecular Psychiatry. 27(11):4781-4789
Subject
Language
English
ISSN
1359-4184
Abstract
Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-beta (A beta) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for A beta ([F-18]AZD4694) and tau ([F-18]MK-6240), as well as CSF GFAP and YKL-40 measures. We observed that higher CSF GFAP levels were associated with elevated A beta-PET but not tau-PET load. By contrast, higher CSF YKL-40 levels were associated with elevated tau-PET but not A beta-PET burden. Structural equation modeling revealed that CSF GFAP and YKL-40 mediate the effects of A beta and tau, respectively, on hippocampal atrophy, which was further associated with cognitive impairment. Our results suggest the existence of distinct astrocyte biomarker signatures in response to brain A beta and tau accumulation, which may contribute to our understanding of the complex link between reactive astrogliosis heterogeneity and AD progression.