1. |
- Ferrari-Souza, J. P., et al.
(författare)
-
Astrocyte biomarker signatures of amyloid-beta and tau pathologies in Alzheimer's disease
- 2022
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27:11, s. 4781-4789
-
Tidskriftsartikel (refereegranskat)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.
|
|