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Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer's disease. 2022
João Pedro Ferrari-Souza, and
Pâmela C L Ferreira, and
Bruna Bellaver, and
Cécile Tissot, and
Yi-Ting Wang, and
Douglas T Leffa, and
Wagner S Brum, and
Andréa L Benedet, and
Nicholas J Ashton, and
Marco Antônio De Bastiani, and
Andréia Rocha, and
Joseph Therriault, and
Firoza Z Lussier, and
Mira Chamoun, and
Stijn Servaes, and
Gleb Bezgin, and
Min Su Kang, and
Jenna Stevenson, and
Nesrine Rahmouni, and
Vanessa Pallen, and
Nina Margherita Poltronetti, and
William E Klunk, and
Dana L Tudorascu, and
Ann D Cohen, and
Victor L Villemagne, and
Serge Gauthier, and
Kaj Blennow, and
Henrik Zetterberg, and
Diogo O Souza, and
Thomas K Karikari, and
Eduardo R Zimmer, and
Pedro Rosa-Neto, and
Tharick A Pascoal
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
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-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for Aβ ([18F]AZD4694) and tau ([18F]MK-6240), as well as CSF GFAP and YKL-40 measures. We observed that higher CSF GFAP levels were associated with elevated Aβ-PET but not tau-PET load. By contrast, higher CSF YKL-40 levels were associated with elevated tau-PET but not Aβ-PET burden. Structural equation modeling revealed that CSF GFAP and YKL-40 mediate the effects of Aβ 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 Aβ and tau accumulation, which may contribute to our understanding of the complex link between reactive astrogliosis heterogeneity and AD progression.
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