Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer's disease

Brain, Behavior, and Immunity
Junling YangKen-ichiro Fukuchi

Abstract

Neuroinflammation is a pervasive feature of Alzheimer's disease (AD) and characterized by activated microglia, increased proinflammatory cytokines and/or infiltrating immune cells. T helper 17 (Th17) cells are found in AD brain parenchyma and interleukin-17A (IL-17A) is identified around deposits of aggregated amyloid β protein (Aβ). However, the role of IL-17A in AD pathogenesis remains elusive. We overexpressed IL-17A in an AD mouse model via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated intracranial gene delivery. AD model mice subjected to injection of a vehicle (PBS) or rAAV5 carrying the lacZ gene served as controls. IL-17A did not exacerbate neuroinflammation in IL-17A-overexpressing mice. We found that IL-17A overexpression markedly improved glucose metabolism, decreased soluble Aβ levels in the hippocampus and cerebrospinal fluid, drastically reduced cerebral amyloid angiopathy, and modestly but significantly improved anxiety and learning deficits. Moreover, the ATP-binding cassette subfamily A member 1 (ABCA1), which can transport Aβ from the brain into the blood circulation, significantly increased in IL-17A-overexpressing mice. In vitro treatment of brain endothelial bEnd.3 cells with IL-17A induced...Continue Reading

Citations

Sep 5, 2018·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Alireza SarkakiSeyedeh Parisa Navabi
Dec 4, 2019·The European Journal of Neuroscience·Caroline NothdurfterThomas C Baghai
Dec 28, 2019·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Fanny M ElahiJoel H Kramer
Jun 26, 2020·Frontiers in Immunology·Jelena MilovanovicNebojsa Arsenijevic
Nov 19, 2019·Frontiers in Aging Neuroscience·Puneet TalwarRachna Agarwal
Sep 9, 2018·Acta Neuropathologica Communications·Sonja RakicDelphine Boche
Nov 21, 2020·Journal of Alzheimer's Disease : JAD·Julio A Flores-CuadraMaria B Carreira
Jan 27, 2021·Annual Review of Pathology·Caitlin S LatimerThomas J Montine
Nov 3, 2020·Frontiers in Aging Neuroscience·Junjue ChenYisheng Zhong
Feb 11, 2021·International Journal of Molecular Sciences·Leonor Jacobo-AlbaveraTeresa Villarreal-Molina
Aug 21, 2021·Essays in Biochemistry·Jared S Katzeff, Woojin Scott Kim

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