Agerelated changes in Alzheimer’s disease-like pathology in male APP/PS1/Tau triple transgenic mice / 中风与神经疾病杂志

ABSTRACT

@#Objective Immunohistochemical methods were used to observe the age-related changes of Alzheimer’s disease-related pathology in the hippocampus and sensory cortex in male APP/PS1/Tau triple transgenic mice aged 2-15 months.Methods Male 3xTg-AD mice were randomly divided into 7 groups according to the age of 2，4，6，8，10，12 and 15 months，with 3 mice in each group as the experimental group；age-matched male C5B7L/6J mice Randomly divided into 7 groups according to the age of 2，4，6，8，10，12 and 15 months，with 3 mice in each group as a control group. The immunohistochemical method was used to detect the pathological age-related changes in the hippocampus and sensory cortex of each mouse brain tissue with age，closely related to Alzheimer’s disease，including Aβ，phosphorylated tau，transgenic products of human tau P301L mutant，astrogliosis，neuron markers.Results Compared with C5B7L/6J mice，the intensity of immunostaining of Aβ cells（6E10），p-tau（AT8，Ser202/Thr205） and tau（HT7） astrocytes（GFAP） in APP/PS1/Tau triple transgenic mice is significantly enhanced，P<0.0001.The hippocampus and sensory cortex of male APP/PS1/Tau triple transgenic mice aged 2-15 months did not have obvious amyloid plaque deposition. The staining degree of Aβ cells in the CA1 area of the hippocampus gradually increased at the age of 8 months，and the staining degree of the sensory cortex remained unchanged，P<0.05. The staining degree of Tau (HT7) in the CA1 area has weak staining at 2 to 6 months of ageand the staining degree remained stable from 6 months to 15 months；The degree of staining in the sensory cortex increased from 2 to 4 months old，and the degree of staining remained stable at 4 to 15 months，P<0.05.The phosphorylation of AT8 in CA1 area began to increase at 6 months，and the phosphorylation of sensory cortex began to increase at 12 months，P<0.05.Astrocytes（GFAP） in CA1 area and sensory cortex area gradually increase in reactivity from 2 months to 15 months. The number of mature neuron markers（NEUN） in CA1 area gradually decreased from 2 months to 6 months，and was stable from 6 months to 15 months. The number of NEUN in CA-3 area gradually decreased from 2 months to 15 months，P<0.05.Conclusion 3xTg-AD mice show a clear interaction between age and phenotype development，which makes it an important tool for studying the role of aging in disease pathogenesis.