Innate immune alterations are elicited in microglial cells before plaque deposition in the Alzheimer's disease mouse model 5xFAD

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Abstract

Alzheimer's disease (AD) is the most common form of dementia characterized by the formation of amyloid plaques (Aβ). Over the last decade, the important role of the innate immune system for the disease development has been established. Chronic activation of microglial cells creates a proinflammatory environment, which is believed to be central for the development of the disease as well as its progression. We used the AD mouse model 5xFAD to investigate if inflammatory alterations are present in microglial cells before plaque deposition. We applied mass spectrometry and bioinformation analysis to elucidate early microglial alterations. Interestingly, we found the cytokines IL1β and IL10 to be elevated in the 5xFAD brain after the formation of Aβ plaque at 10 weeks only. Using mass spectrometry analysis of microglial cells with bioinformation analysis, we found JAK/STAT, p38 MAPK and Interleukin pathways affected in microglial cells before plaque deposition at 6 weeks. At 10 weeks, GO analysis showed affected pathways related to interferon-gamma regulation and MAPK pathways. Our study points toward early inflammatory changes in microglial cells even before the accumulation of Aβ.

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  • Neurosciences
Original languageEnglish
Article number1550
JournalScientific Reports
Volume8
Issue number1
Publication statusPublished - 2018 Dec 1
Publication categoryResearch
Peer-reviewedYes