Aβ Deposition In Cortex Research Articles

Effects of on behavior and blood-brain barrier in Alzheimer's disease mice.

To investigate the effects of on behavior and blood brain barrier (BBB) in Alzheimer's disease mice. Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, low-dose group and high-dose group. Saline, and 12 g·kg·d were given to each group by continuous gavage once a day for respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Compared with model mice, activities of daily live were significantly improved in low-dose and high-dose groups (both <0.01), the fear memory ability was significantly increased in high-dose group (<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly in high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region in low-dose group also decreased (all <0.05). The proportions of CD34 positive area of cortex in low and high dose groups increased, the percentage of fibrinogen positive area decreased (all <0.05). The proportion of CD34 positive area in hippocampal CA1 region in high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both <0.05). especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.

Treatment with Bifidobacteria can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice.

BackgroundAlzheimer’s disease (AD), being a complex disorder, is affected either by genetic or environmental factors or both. It is observed that there is an excessive accumulation of amyloid β (Aβ) in the extracellular space of the brain. AD is the first neurodegenerative disease in the elderly, and so far there is no effective treatment. In recent years, many studies have reported that Alzheimer’s disease has a relationship with gut microflora, indicating that regulating gut microbiota could offer therapeutic intervention for AD. This study explored the effect Bifidobacteria has in averting AD.MethodsWT and APP/PS1 mice were used for the experiments. The mice were randomly assigned to four groups: WT group, WT + Bi group, AD group (APP/PS1 mouse) and AD + Bi group (Bifidobacteria-treated APP/PS1 mouse). Treatment with Bifidobacteria lasted for 6 months and mice were prepared for immunohistochemistry, immunofluorescence, Thioflavin S staining, Western blotting, PCR and Elisa quantitative assay.ResultsThe results show that after 6 months of treatment with Bifidobacteria signiis to be lesficantly reduces Aβ deposition in cortex and hippocampus of AD mice. The level of insoluble Aβ in the hippocampus and cortex of AD+Bi mice was decreased compared with AD mice. Meanwhile, a significant decrease in the level of soluble Aβ in the cortex of AD+Bi mice but not in the hippocampus was observed. The activation of microglia and the release of inflammatory factors were also determined in this study. From the results, Bifidobacteria inhibited microglial activation and reduced IL-1β, TNF-α, IL-4, IL-6 and INF-γ release. Altogether, these results implied that Bifidobacteria can alleviate the pathological changes of AD through various effects.

ApoE mimetic improves pathology and memory in a model of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia and is characterized pathologically by Aβ plaques. Current treatments are purely symptomatic despite decades of intensive research interest. Notably, patients with the APOE4 allele are at increased risk for developing AD. One hypothesis regarding the mechanism by which the APOE4 allele might increase AD risk is loss of adaptive function, raising the possibility that the exogenous administration of apoE mimetics would have therapeutic effects. In this study, we utilized a previously characterized murine model of AD containing human APP, PS1 and APOE4TR, the APP/PS1/APOETR mouse. We treated male APP/PS1/APOETR mice with the apoE mimetic CN-105 or vehicle for 40d, beginning either at 14–18 or 25–28 weeks of age. After termination of treatment we tested animals in both Morris water maze and contextual fear conditioning, and examined soluble Aβ by biochemistery and Aβ deposition in cortex by unbiased stereology. We found that transient treatment with CN-105 for 40d beginning at 14–18 weeks reduced Aβ pathology and rescued memory deficits in male APP/PS1/APOETR mice. Notably, delaying treatment onset to 25–28 weeks did not produce as robust an effect. These results suggest CN-105 treatment in a mouse model of AD results in a reduction in AD pathology and improved behavioral outcomes when administered early in the course of disease. As CN-105 has an excellent safety profile and is already in clinical trials, these findings raise the possibility that CN-105 represents a novel and translatable therapeutic strategy for AD.