Age-related Myelin Changes In The 5XFAD Mouse Model

Background:Lots of studies have shown abnormal myelin in AD, but it is controversial whether myelin damage appears in very early stage of AD. Electron microscopy is an extremely sensitive high-resolution tool that can allow us to observe the dynamic characteristics of myelin changes throughout a time period (several months) at early stages of AD.Objective:To investigate the age-related myelin change and the characteristics of behavioral tests in 5XFAD mice.Methods:Memory function of 5XFAD was detected by Morris water maze test and we made qualitative and quantitative analysis of electron microscopy graphs from regions (PFC, RSG, CA1 and Ent) in 5XFAD mice at 1,2 and 3 months age.Results:Some abnormal sheaths, such as myelin with loose sheath and axons surrounded by excess cytoplasm in the inner loop, ballooned sheaths, axons surrounded by two myelin sheaths, abnormal myelin out folding, myelin breakdown and other myelin abnormalities were observed in 5XFAD mice. Otherwise, our results revealed myelin deficits, thinner myelin sheath at early stage of AD and an age-related increase in myelin deficits in 5XFAD mice. In Morris water maze test, we discovered that spatial learning ability decreased in 5XFAD mice at 2 months age while spatial reference memory decreased in 5XFAD mice at all ages.Conclusions Myelin change has appeared at very early stage of AD in 5XFAD mice, and this change is associated with age and cognitive impairment.