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.