Objective      To compare the expression profile of p75 neurotrophin receptor (p75NTR) and senile plaque formation in a mouse model of Alzheimer’s disease (AD).       Methods      Brain sections and homogenates from male B6C3-Tg (APPSwePSEN1dE9) 85Dbo/J transgenic mice and their male wild type littermates aged 3

6

or 9 months old (n=6 for each age) were subjected in this study. The senile plaques

degenerated p75NTR positive neurites and their colocalization were illustrated using Congo red

immunohistochemical and fluorescence staining. ELISA and Western blot analysis were applied to detect the expression level of total Aβ and p75NTR in brain homogenates. Confocal microscopy was used to observe the special distribution of senile plaque

p75NTR positive and negative degenerated neurites.       Results      In the brain of AD transgenic mice

the senile plaques appeared firstly at 6 months in the cortex and hippocampus

where the burden of senile plaques increased at 9 months. It showed an age-dependent increase of Aβ in both Congo red staining and ELISA measures. Meanwhile

the onset of degenerated p75NTR positive neurites occurred as early as 3 months when senile plaques were not yet formed

mainly in the cortex and hippocampus. The expression of p75NTR was elevated with the increase of age in both AD transgenic mice and their wild type littermates

which was even higher in transgenic mice. Confocal microscopy showed that p75NTR positive degenerated neurites located in the center of senile plaques while p75NTR negative degenerated neurites were at the periphery of the plaques.       Conclusion      p75NTR expression increases with aging

and is further activated by Aβ. The degenerated p75NTR positive neurites appear much earlier in the cortex and hippocampus than the formation of Aβ plaques

suggesting that p75NTR may promote the initiation of senile plaque formation.