Analysis of CX3CR1 haplodeficiency in male and female APPswe/PSEN1dE9 mice along Alzheimer disease progression

Microglia, the resident immune cells of the brain, have recently emerged as key players in Alzheimer Disease (AD) pathogenesis, but their roles in AD remain largely elusive and require further investigation. Microglia functions are readily altered when isolated from their brain environment, and microglia reporter mice thus represent valuable tools to study the contribution of these cells to neurodegenerative diseases such as AD. The CX3CR1(+/eGFP) mice is one of the most popular microglia reporter mice, and has been used in numerous studies to investigate in vivo microglial functions, including in the context of AD research. However, until now, the impact of CX3CR1 haplodeficiency on the typical features of Alzheimer Disease has not been studied in depth. To fill this gap, we generated APP(swe)/PSEN1(dE9):CX3CR(1+/eGFP) mice and analyzed these mice for Alzheimer's like pathology and neuroinflammation hallmarks. More specifically, using robust multifactorial statistical and multivariate analyses, we investigated the impact of CX3CR1 deficiency in both males and females, at three typical stages of the pathology progression: at early stage when Amyloid-beta (A beta) deposition just starts, at inter mediate stage during A beta accumulation phase and at more advanced stages when A beta plaque number stabilizes. We found that CX3CR1 haplodeficiency had little impact on the progression of the pathology in the APP(swe)/PSEN1(dE9) model and demonstrated that the APP(swe)/PSEN1(dE9):CX3CR1(+/eGFP) line is a relevant and useful model to study the role of microglia in Alzheimer Disease. In addition, although A beta plaques density is higher in females compared to age-matched males, we show that their glial reaction, inflammation status and memory deficits are not different.

Automated summary

This study investigated the impact of CX3CR1 haplodeficiency on Alzheimer's disease pathology progression in a mouse model. The results showed that CX3CR1 deficiency had little effect on the pathology progression, but the APP(swe)/PSEN1(dE9):CX3CR1(+/eGFP) mouse line is a useful model for studying the role of microglia in Alzheimer's disease. Additionally, despite higher A beta plaque density in females, their glial reaction, inflammation status and memory deficits were not different from age-matched males.