The role of S100a9 in the pathogenesis of Alzheimer's disease: the therapeutic effects of S100a9 knockdown or knockout.

Neuroinflammation is one of the important pathogenic features of Alzheimer's disease (AD). Recently, S100a9 was found to be increased within neuritic plaques and reactive glia and was proposed to participate in the inflammation associated with the pathogenesis of AD. Our study showed that S100a9 expression was increased in the brains of AD mice and AD patients. In Tg2576 mice, knockdown by short hairpin RNA or knockout of the S100a9 gene significantly reduced the neuropathology, greatly improved the learning and memory impairment and reduced the amount of Aβ and APP-CTs by increasing neprilysin and decreasing BACE activity. These results clearly show that the upregulation of the S100a9 gene plays an important role in the neuropathology and memory impairment in AD, suggesting that the knockdown and knockout of this gene have a great therapeutic potential for AD.