Intestinal microbial dysbiosis aggravates the progression of Alzheimer’s disease in Drosophila

Shih-Cheng Wu, Zih-Syuan Cao, Kuo-Ming Chang and Jyh-Lyh Juang ()
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Shih-Cheng Wu: National Health Research Institutes
Zih-Syuan Cao: National Health Research Institutes
Kuo-Ming Chang: Hsinchu Mackay Memorial Hospital
Jyh-Lyh Juang: National Health Research Institutes

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract Neuroinflammation caused by local deposits of Aβ42 in the brain is key for the pathogenesis and progression of Alzheimer’s disease. However, inflammation in the brain is not always a response to local primary insults. Gut microbiota dysbiosis, which is recently emerging as a risk factor for psychiatric disorders, can also initiate a brain inflammatory response. It still remains unclear however, whether enteric dysbiosis also contributes to Alzheimer’s disease. Here we show that in a Drosophila Alzheimer’s disease model, enterobacteria infection exacerbated progression of Alzheimer’s disease by promoting immune hemocyte recruitment to the brain, thereby provoking TNF-JNK mediated neurodegeneration. Genetic depletion of hemocytes attenuates neuroinflammation and alleviated neurodegeneration. We further found that enteric infection increases the motility of the hemocytes, making them more readily attracted to the brain with an elevated oxidative stress status. This work highlights the importance of gut–brain crosstalk as a fundamental regulatory system in modulating Alzheimer’s disease neurodegeneration.

Date: 2017
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DOI: 10.1038/s41467-017-00040-6

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