| Literature DB >> 35948658 |
Eduardo R Zimmer1,2,3, Pedro Rosa-Neto4, Tharick A Pascoal5, João Pedro Ferrari-Souza6,1, Pâmela C L Ferreira6, Bruna Bellaver6, Cécile Tissot6,4, Yi-Ting Wang4, Douglas T Leffa7, Wagner S Brum1,8,9, Andréa L Benedet4,8, Nicholas J Ashton8,9,10,11, Marco Antônio De Bastiani1, Andréia Rocha1, Joseph Therriault4, Firoza Z Lussier4, Mira Chamoun4, Stijn Servaes4, Gleb Bezgin4, Min Su Kang4, Jenna Stevenson4, Nesrine Rahmouni4, Vanessa Pallen4, Nina Margherita Poltronetti4, William E Klunk6, Dana L Tudorascu6, Ann D Cohen6, Victor L Villemagne6, Serge Gauthier4, Kaj Blennow8,9, Henrik Zetterberg8,9,12,13,14, Diogo O Souza1, Thomas K Karikari6,8,9.
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-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.Entities:
Year: 2022 PMID： 35948658 DOI： 10.1038/s41380-022-01716-2
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 13.437