Effects of Microglial Cytokines on Alzheimer’s Disease-Related Phenomena

Article type: Research Article

Authors: Ji, Yan^{a; b; 1} | Wang, Xiaowan^{a; c; 1} | Kalicki, Colin^a | Menta, Blaise W.^a | Baumgardner, Megan^{a; c} | Koppel, Scott J.^{a; d} | Weidling, Ian W.^{a; d} | Perez-Ortiz, Judit^{a; c} | Wilkins, Heather M.^{a; c} | Swerdlow, Russell H.^{a; c; d; e; *}

Affiliations: [a] University of Kansas Alzheimer’s Disease Center, Kansas, USA | [b] Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China | [c] Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA | [d] Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA | [e] Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA

Correspondence: [*] Correspondence to: Russell H. Swerdlow, Landon Center on Aging, MS 2012, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. Tel.: 1-913-588-0555; Fax: 1-913-588-0681; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Recent association studies indicate several genes highly expressed by microglia influence Alzheimer’s disease (AD) risk, which suggests microglial function contributes to this disease. Here, we evaluated how one component of microglial function, cytokine release, affects AD-related phenomena. First, we used a 3-hour lipopolysaccharide (LPS) treatment to activate mouse BV2 microglial cells. Next, we removed the LPS-containing medium, added LPS-free medium, and after 6 hours collected the medium conditioned by the activated BV2 microglial cells. We then exposed human neuronal SH-SY5Y cells to the conditioned medium for 24 hours. At the end of the 24-hour exposure, we assessed amyloid-β protein precursor (AβPP), tau, apolipoprotein E (ApoE), and lipid status. The amount of AβPP was unaffected, although a slight decrease in soluble AβPPα suggested a subtle reduction in AβPP non-amyloidogenic processing occurred. Tau mRNA increased, but total and phosphorylated tau levels were unchanged. ApoE mRNA increased, while ApoE protein levels were lower. Per cell lipid droplet number decreased and lipid oxidation increased. These results show cytokine release by activated microglial cells can influence specific AD-relevant physiologies and pathologies.

Keywords: Alzheimer’s disease, ApoE, inflammation, lipid droplets, microglia

DOI: 10.3233/JAD-180820

Journal: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1021-1034, 2019