• Zhou Wu, Li Sun, Sadayuki Hashioka, Sheng Yu, Claudia Schwab, Ryo Okada, Yoshinori Hayashi, Patrick L McGeer, and Hiroshi Nakanishi.
• Faculty of Dental Sciences, Department of Aging Science and Pharmacology, Kyushu University, Fukuoka, Japan. Electronic address: zhouw@dent.kyushu-u.ac.jp.
• Neurobiol. Aging. 2013 Dec 1; 34 (12): 2715-25.

AbstractAlthough chromogranin A (CGA) is frequently present in Alzheimer's disease (AD), senile plaques associated with microglial activation, little is known about basic difference between CGA and fibrillar amyloid-β (fAβ) as neuroinflammatory factors. Here we have compared the interleukin-1β (IL-1β) production pathways by CGA and fAβ in microglia. In cultured microglia, production of IL-1β was induced by CGA, but not by fAβ. CGA activated both nuclear factor-κB (NF-κB) and pro-caspase-1, whereas fAβ activated pro-caspase-1 only. For the activation of pro-caspase-1, both CGA and fAβ needed the enzymatic activity of cathepsin B (CatB), but only fAβ required cytosolic leakage of CatB and the NLRP3 inflammasome activation. In contrast, fAβ induced the IL-1β secretion from microglia isolated from the aged mouse brain. In AD brain, highly activated microglia, which showed intense immunoreactivity for CatB and IL-1β, surrounded CGA-positive plaques more frequently than Aβ-positive plaques. These observations indicate differential pathways for the microglial IL-1β production by CGA and fAβ, which may aid in better understanding of the pathological significance of neuroinflammation in AD.Copyright © 2013 Elsevier Inc. All rights reserved.

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