The characteristics of astrocyte on Aβ clearance altered in Alzheimer's disease were reversed by anti-inflammatory agent (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate.
Astrocytes are closely related to the amyloid-β (Aβ) deposition in the brain and play crucial roles in Alzheimer's disease (AD) pathology. Meanwhile, inflammation in the CNS has been increasingly demonstrated as a prominent hallmark in AD. Our data from animal models and subjects with Alzheimer's disease (AD) showed GFAP immunoreactivity altered in different stage of AD and had a positive correlation with neprilysin (NEP), suggesting astrocytes might take a protective role in pathogenetic course of AD. Here, we investigate the role of astrocyte in the mechanism of Aβ removal. ELISA and western blotting were performed to determine the ability of astrocyte to clear Aβ1-42. In this study, we demonstrated that cultured astrocytes removed extracellular oligomeric Aβ. However, cultured astrocytes from an AD mouse model showed less capacity to clear extracellular Aβ42but with hyper-expression of NEP protein than normal astrocytes. In addition, LPS-induced inflammation rather than continuous Aβ stimuli inhibited the capacity of Aβ clearance by astrocytes indicating that inflammation possibly contributed to astrocytic dysfunction. Lastly, HOEC which exhibited anti-inflammatory effects restored the capacity of injured or aged astrocytes to clear Aβ. In conclusion, astrocytes have been shown to exert a direct role in Aβ clearance and undergo functional impair associated with inflammation in the pathogenesis of AD. Therefore, anti-inflammatory treatments aimed at restoring astrocyte functions may represent an appropriate approach to treat AD.
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology 130 Meilong Road, Shanghai 200237, China.
Rui-Xuan
RX
Liu
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology 130 Meilong Road, Shanghai 200237, China.
Cui
C
Huang
Department of Nutrition and Food Health, School of Public Health, Wuhan UniversityWuhan, China; Rush Alzheimer's Disease Center, Rush University Medical CenterChicago, IL, USA.
David A
DA
Bennett
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology 130 Meilong Road, Shanghai 200237, China.
Honglin
H
Li
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology 130 Meilong Road, Shanghai 200237, China.
Rui
R
Wang
Alzheimer’s disease; Aβ clearance; HOEC; astrocyte; inflammation; neprilysin