biostudies-literatureFerrari-Souza JPMinistry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development)European Research CouncilNIA NIH HHSFondation Brain Canada (Fondation Neuro Canada)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazilian Federal Agency for the Support and Evaluation of Graduate Education)Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec)U.S. Department of Health & Human Services | National Institutes of Health (NIH)Alzheimer's AssociationGouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)4781-4789https://www.ebi.ac.uk/biostudies/studies/S-EPMC9734046biostudies-literatureUnknown27(11)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 Molecular psychiatryAstrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer's disease.PMC9734046R01 AG073267NIRP-12-2592452020-VICO-279314AACSF-20-648075435642/2018-9NIRG-12-92090R01AG073267R01AG075336R01 AG075336MOP-11-51-317209313339768171288887.627297/2021-00312410/2018- 2Kang MSKlunk WEGauthier SFerrari-Souza JPZimmer ERVillemagne VLStevenson JRocha AZetterberg HLeffa DTDe Bastiani MAChamoun MPascoal TABenedet ALPoltronetti NMTherriault JRahmouni NCohen ADServaes SFerreira PCLBellaver BRosa-Neto PTissot CTudorascu DLSouza DOAshton NJBrum WSBezgin GPallen VWang YTKarikari TKBlennow KLussier FZfalseAstrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer's disease.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 2022-01-01T00:00:00Z2022 Nov2026-04-12T15:07:54.106Z2025-04-05T21:25:41.624ZS-EPMC97340463594865810.1038/s41380-022-01716-2