Abstract:Objective: To investigate the effect of Aβ on lysosomes in neurons and microglia of Alzheimer’s disease (AD) model mice. Methods: Six 6-month-old APP/PS1 double transgenic AD mice and six wild type (WT) mice were selected to observe the expression of neurons and microglia, as well as the co-expression of neurons, microglia and lysosomes by immunofluorescence staining. Western blot was used to detect the expression of autophagy related proteins. After SH-SY5Y cells were treated with Aβ25-35, adenovirus overexpressed transcription factor EB (TFEB) was intervened for 72 h. The levels of TFEB and lysosomal markers were detected by Western blot. Results: Compared with wild-type mice, the expression of LC3 and p62 in AD transgenic mice at 6 months old increased (t=4.976, P=0.008; t=4.463, P=0.011), and the lysosomal marker protein LAMP1 decreased significantly (t=14.91, P=0.000 1). In AD model group, neurons were significantly lost, microglia were significantly proliferated and lysosome expression was significantly decreased. Compared with wild-type mice, the expression of p-mammalian target of rapamycin (p-mTOR) /mTOR protein in AD transgenic mice was significantly increased (t=5.501, P=0.005), and the expression of TFEB protein was significantly decreased (t=5.899, P=0.004). Aβ25-35 down regulated the protein levels of TFEB and Lamp1 in SH-SY5Y cells (t=10.94, P<0.001; t=17.22, P<0.001). Overexpression of TFEB significantly increased the protein level of lysosomal marker Lamp1 (t=5.136, P<0.01). Conclusion: Aβ can decrease lysosomes in neurons and microglia of AD model mice, which may act by inhibiting mTOR/TFEB signaling pathway.
