Presenter of 1 Presentation
CSF GFAP IS ASSOCIATED WITH BRAIN AMYLOID-BETA WHILE CSF YLK-40 IS ASSOCIATED WITH BRAIN TAU IN ALZHEIMER’S DISEASE
Abstract
Aims
To test the association between amyloid-β (Aβ) and tau pathologies with fluid glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) across the Alzheimer’s disease (AD) spectrum.
Methods
We assessed 77 cognitively unimpaired and 48 cognitively impaired (30 mild cognitive impairment and 18 AD dementia) participants (age > 50 years) from the McGill TRIAD cohort. Individuals had available positron emission tomography (PET; [18F]AZD4694 for Aβ and [18F]MK6240 for tau tangles) and magnetic resonance imaging, as well as cerebrospinal fluid (CSF) astrocyte GFAP and YKL-40 markers. Cognition was assessed with the Mini-Mental State Examination.
Results
Voxel-wise linear regression revealed that higher GFAP levels but not YKL-40 levels were associated with increased Aβ-PET load in typical AD brain regions independently of tau pathology (Figure 1). On the other hand, higher YKL-40 levels but not GFAP levels were positively associated with tau-PET uptake in brain regions of early and late tau tangle accumulation independently of Aβ pathology (Figure 2). Structural equations models demonstrated that GFAP mediates the association between Aβ and hippocampal atrophy, while YKL-40 mediates the association between tau and hippocampal atrophy.
Conclusions
We showed for the first time in living individuals that two of the most important astrocyte reactivity markers, GFAP and YKL-40, are differentially associated with AD pathological hallmarks. While GFAP better represents Aβ pathology, YKL-40 better represents tau pathology. Our findings support that understanding the role of the different astrocyte phenotypes in the development of AD may shed light on the complex link between brain proteinopathies and downstream disease progression.