[Verification of a sporadic Alzheimer disease model in SORL1 gene knockout mice].

OBJECTIVE: To compare the behavioral and pathological features of SORL1 gene knockout mice with those of normal mice and APP/PSE1 mice to verify the feasibility of using SORL1 knockout mice as a model of sporadic Alzheimer disease. METHODS: SORL1 gene of fertilized mouse eggs were edited using Crispr/Case9 technique. SORL1-/- mice were screened and identified by detecting the DNA sequence, and Western blotting was used to detect the expression of SORL1. SORL1-/- mice, control mice and APP/PSE1 mice all underwent Morris water maze test to assess their learning and memory abilities with positioning navigation and space exploration experiments. The expression of APP and Aß in the brain of the mice was detected using immunohistochemistry and Western blotting, respectively. RESULTS: DNA sequencing showed CAAT deletion in SORL1 gene in two chromosomes of SORL1-/- mice, and the control mice had intact SORL1 gene without the deletion; Western blotting did not detect the expression of the SORL1 in the brain of SORL1-/- mice. Morris water maze test showed that in positioning navigation experiment, the average avoidance latency was similar between SORL1-/- mice and APP/PSE1 mice (P>0.05) but increased significantly in both mice as compared with the control group (P<0.05); similar results were obtained in the space exploration experiment. Immunohistochemistry and Western blotting revealed significantly increased APP and Aß expression in the brain tissue of both SORL1-/- mice and APP/PSE1 mice compared with the control mice without significant differences between the two transgenic mice. CONCLUSION: SORL1-/- mice exhibit similar behavioral and pathological changes with APP/PSE1 mice and can be used as a model of sporadic Alzheimer's disease.

[Protective effect of butylphthalide in a cell model of Alzheimer's disease induced by Aß25-35 in Neuro 2a cells].

OBJECTIVE: To study the protective effect of butylphthalide in a cell model of Alzheimer's disease(AD) induced by Aß25-35 in Neuro 2a (N2a) cells. METHODS: N2a cells were divided into AD group, butylphthalide (NBP) group and control group. AD cell model was established by adding 20 µmol/L Aß25-35 to cultured N2a cells. The cells in NBP group were treated with 0.1, 1, 10, or 100 µmol/L NBP 4 h prior to treatment with 20 µmol/L Aß25-35. The cell viability were determined by MTT assay, the cell apoptotic rate were detected by AnnexinV-FITC flow cytometry, and the cell morphological changes were observed under inverted phase contrast microscope. The expression of TNF-α and IL-1ß mRNA were determined by qRT-PCR. RESULTS: Compared with those in the control group, the number of adherent cells was significantly decreased, neurite structures were reduced, and the cell viability was decreased, while the apoptotic rate and expressions of TNF-α and IL-1ß mRNA were increased in AD group (P<0.05). Compared with that in AD group, the number of adherent cells was increased in NBP group and the cell morphology was similar to the normal control cells. The cell viability of N2a cells was increased in NBP group with decreased apoptotic rate and expression of TNF-αand IL-1ß mRNA (P<0.05). CONCLUSION: Butylphthalide can protect against AD in the cell model induced by Aß25-35 possibly by inhibiting the expression of inflammatory cytokines.

[Correlation between serum adiponectin level and cognitive function in patients with Alzheimer's disease].

OBJECTIVE: To investigate serum adiponectin level in patients with Alzheimer's disease (AD) and its correlation with the patients' cognitive function. METHODS: This case-control study was conducted in 90 patients with a highly probable diagnosis ofAD, who were divided into mild, moderate and severe group saccording to the MMSE score. Ninety healthy subjects matched for age and gender with the AD patients were selected as the control group. The serum levels ofadiponectin in the participants were detected using enzyme-linked immunosorbent assay. RESULTS: Serum adiponectin level was significantly lower in the AD group than in the control group (P<0.05). Of the 3 subgroups of the AD patients, the moderate and severe AD groups showed significantly lower serum adiponectin level sthan the control group (P<0.05), but the difference in adiponectin levels was not significant between the mild AD group and the control group (P>0.05); serum adiponectin levels also differed significantly among the 3 subgroups of AD patients (P<0.05). Serum adiponectin level was positively correlated with the MMSE score in the AD patients (r=0.683, P<0.001). CONCLUSION: Serum adiponectin levels are reduced in AD patients and associated with the degree of cognitive impairment.