Quercetin-3-O-Glucuronide Alleviates Cognitive Deficit and Toxicity in Aß1-42 -Induced AD-Like Mice and SH-SY5Y Cells.

SCOPE: Alzheimer's disease (AD) is characterized by amyloid-ß (Aß) related imbalance, Tau-hyperphosphorylation, and neuroinflammation, in which Aß and neuroinflammation can induce brain insulin resistance (IR). Gut microbiome disorder is correlated with inflammation in AD. As of yet, there are no effective treatments clinically. Thus, it is focused on the potential benefit of quercetin-3-O-glucuronide (Q3G), a pharmacologically active flavonol glucuronide, on AD treatment by regulating brain IR and the gut microbiome. METHODS AND RESULTS: AD mice model built through intracerebroventricular injection of Aß1-42 and AD cell model developed through the SH-SY5Y cell line and Aß1-42 are used to explore the protective effects of Q3G on AD. Neurobehavioral test, brain insulin signaling pathway, and high-throughput pyrosequencing of 16S rRNA are assessed. Data show that Q3G attenuates neuroinflammation and brain IR in Aß1-42 -injected mice and relieves apoptosis in Aß1-42 -treated SH-SY5Y cells by interrupting the downstream insulin signaling. Q3G ameliorates Aß accumulation and Tau phosphorylation, restores CREB and BDNF levels in the hippocampus , and reverses Aß1-42 -induced cognitive impairment. Besides, Q3G restores Aß1-42 -induced reduction of short-chain fatty acids (SCFAs) and gut microbiota dysbiosis. CONCLUSION: Q3G can alleviate brain IR through directly acting on the brain or modulating the gut-brain axis, ultimately to relieve Aß1-42 -induced cognitive dysfunction.

Yeast ß-glucan alleviates cognitive deficit by regulating gut microbiota and metabolites in Aß1-42-induced AD-like mice.

Alzheimer's disease (AD) is a neurodegenerative disease that remarkably imposes a huge global public health burden. Yeast ß-glucans have been incorporated in functional foods and used in prophylactic applications owing to their biological effects. However, few studies had investigated the effects of yeast ß-glucans on neurodegenerative diseases. Here, gut microbiota and metabolites SCFAs were analyzed through high-throughput 16S rRNA gene sequencing and GC-MS, respectively. Results indicated that yeast ß-glucans could prominently shape the intestinal flora and produce SCFAs. Aß1-42-induced AD mice treated with small-molecular yeast ß-glucan (S-ß-Glu) or macro-molecular yeast ß-glucan (M-ß-Glu) exhibited evident alterations of the composition of the gut microbiota, especially in some beneficial bacteria and inflammatory-related bacteria such as Lactobacillus, Bifidobacterium, Desulfovibrio, Oscillibacter, Mucispirillum, Alistipes, Anaerotruncus, and Rikenella. M-ß-Glu regulated gut microbiota act as prebiotics better than S-ß-Glu. Correlation analysis demonstrated the key microbiota closely associated with AD-related pathologies and cognition. Moreover, M-ß-Glu and S-ß-Glu ameliorated neuroinflammation and brain insulin resistance (IR), which played a central role in the process of AD pathology. This study broadened the underlying applications of yeast ß-glucans as a novel dietary supplementation to prevent early-stage pathologies associated with AD by regulating gut microbiota and the potential mechanism might be ameliorating brain IR.

Association of plasma ß-amyloid 40 and 42 concentration with type 2 diabetes among Chinese adults.

AIMS/HYPOTHESIS: There is evidence for a bidirectional association between type 2 diabetes and Alzheimer's disease. Plasma ß-amyloid (Aß) is a potential biomarker for Alzheimer's disease. We aimed to investigate the association of plasma Aß40 and Aß42 with risk of type 2 diabetes. METHODS: We performed a case-control study and a nested case-control study within a prospective cohort study. In the case-control study, we included 1063 newly diagnosed individuals with type 2 diabetes and 1063 control participants matched by age (±3 years) and sex. In the nested case-control study, we included 121 individuals with incident type 2 diabetes and 242 matched control individuals. Plasma Aß40 and Aß42 concentrations were simultaneously measured with electrochemiluminescence immunoassay. Conditional logistic regression was used to evaluate the association of plasma Aß40 and Aß42 concentrations with the likelihood of type 2 diabetes. RESULTS: In the case-control study, the multivariable-adjusted ORs for type 2 diabetes, comparing the highest with the lowest quartile of plasma Aß concentrations, were 1.97 (95% CI 1.46, 2.66) for plasma Aß40 and 2.01 (95% CI 1.50, 2.69) for plasma Aß42. Each 30 ng/l increment of plasma Aß40 was associated with 28% (95% CI 15%, 43%) higher odds of type 2 diabetes, and each 5 ng/l increment of plasma Aß42 was associated with 37% (95% CI 21%, 55%) higher odds of type 2 diabetes. Individuals in the highest tertile for both plasma Aß40 and Aß42 concentrations had 2.96-fold greater odds of type 2 diabetes compared with those in the lowest tertile for both plasma Aß40 and Aß42 concentrations. In the nested case-control study, the multivariable-adjusted ORs for type 2 diabetes for the highest vs the lowest quartile were 3.79 (95% CI 1.81, 7.94) for plasma Aß40 and 2.88 (95% CI 1.44, 5.75) for plasma Aß42. The multivariable-adjusted ORs for type 2 diabetes associated with each 30 ng/l increment in plasma Aß40 and each 5 ng/l increment in plasma Aß42 were 1.44 (95% CI 1.18, 1.74) and 1.47 (95% CI 1.15, 1.88), respectively. CONCLUSIONS/INTERPRETATION: Our findings suggest positive associations of plasma Aß40 and Aß42 concentration with risk of type 2 diabetes. Further studies are warranted to elucidate the underlying mechanisms and explore the potential roles of plasma Aß in linking type 2 diabetes and Alzheimer's disease.