Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer's disease.
João Pedro Ferrari-SouzaPâmela C L FerreiraBruna BellaverCécile TissotYi-Ting WangDouglas T LeffaWagner S BrumAndréa L BenedetNicholas J AshtonMarco Antônio De BastianiAndreia S RochaJoseph TherriaultFiroza Z LussierMira ChamounStijn ServaesGleb BezginMin Su KangJenna StevensonNesrine RahmouniVanessa PallenNina Margherita PoltronettiWilliam E KlunkDana L TudorascuAnn D CohenVictor L VillemagneSerge GauthierKaj BlennowHenrik ZetterbergDiogo O SouzaJonathan M SchottEduardo R ZimmerPedro Rosa-NetoTharick Ali PascoalPublished in: Molecular psychiatry (2022)
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 ([ 18 F]AZD4694) and tau ([ 18 F]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.
Keyphrases
- cerebrospinal fluid
- positron emission tomography
- computed tomography
- pet ct
- pet imaging
- white matter
- resting state
- end stage renal disease
- cerebral ischemia
- cognitive impairment
- chronic kidney disease
- newly diagnosed
- functional connectivity
- high resolution
- single cell
- ejection fraction
- cognitive decline
- peritoneal dialysis
- spinal cord injury
- dna methylation
- contrast enhanced
- gene expression
- blood brain barrier
- subarachnoid hemorrhage
- photodynamic therapy
- protein protein
- ionic liquid