IntroductionAlzheimer’s disease (AD) is the most common form of dementia worldwide. The biological mechanisms underlying the pathogenesis of AD aren’t completely clear. Studies have shown that the gut microbiota could be associated with AD pathogenesis; however, the pathways involved still need to be investigated.AimsTo explore the possible pathways of the involvement of gut microbiota in AD pathogenesis through metabolites and to identify new AD biomarkers.MethodsSeven-month-old APP/PS1 mice were used as AD models. The Morris water maze test was used to examine learning and memory ability. 16S rRNA gene sequencing and widely targeted metabolomics were used to identify the gut microbiota composition and fecal metabolic profile, respectively, followed by a combined analysis of microbiomics and metabolomics.ResultsImpaired learning abilities were observed in APP/PS1 mice. Statistically significant changes in the gut microbiota were detected, including a reduction in β-diversity, a higher ratio of Firmicutes/Bacteroidota, and multiple differential bacteria. Statistically significant changes in fecal metabolism were also detected, with 40 differential fecal metabolites and perturbations in the pyrimidine metabolism. Approximately 40% of the differential fecal metabolites were markedly associated with the gut microbiota, and the top two bacteria associated with the most differential metabolites were Bacillus firmus and Rikenella. Deoxycytidine, which causes changes in the pyrimidine metabolic pathway, was significantly correlated with Clostridium sp. Culture-27.ConclusionsGut microbiota may be involved in the pathological processes associated with cognitive impairment in AD by dysregulating pyrimidine metabolism. B. firmus, Rikenella, Clostridium sp. Culture-27, and deoxyuridine may be important biological markers for AD. Our findings provide new insights into the host-microbe crosstalk in AD pathology and contribute to the discovery of diagnostic markers and therapeutic targets for AD.
This study was to explore the effect of nanoparticles on the cognitive function, learning and memory ability (LMA) of Alzheimer’s disease (AD) rats, and to analyze the changes on magnetic resonance (MR) image. Specifically, the TGN nanoparticles loading H102 (TGN-NP-H102) were prepared, and characterized first. The sprague-dawley (SD) rats were selected as the research subjects, and the AD model was constructed. They were divided into a Sham group (normal SD rats, group A), an AD model group (group B), an H102 group (treated with H102 drugs based on AD model, group C), and a TGN-NP-H102 group (treated with TGN-NP-H102 nanoparticles based on AD model, group D). The changes in T2 value in hippocampal CA1 area (T2-CA1) were analyzed, and the changes in cognitive function and LMA were tested with the Morris water maze experiment (Morris experiment). The results revealed that, the average PS (APS) of TGN-NP-H102 nanoparticles was 122.9±2.8 nm, and its average Zeta potential (AZP) was -28.8±0.2 mV. In group A, the TGN-NP-H102 nanoparticles still remained in the brain tissue homogenate by 74.3 ±4.8% after 10 hours, and the drug-release rate was 53.2 ± 3.2%. After 30 days of treatment, the T2-CA1 value of group D was lower (P <0.05), and the average escape latency (AEL) and swimming distance in the Morris experiment were shorter versus group B (P < 0.05). It indicated that, the brain-targeted TGN-NP-H102 nanoparticles prepared could act on the hippocampus of AD rats, and improve their LMA.
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