Ameliorative effects of probiotics in AlCl3-induced mouse model of Alzheimer's disease.

In recent years, gut microbiome alterations have been linked with complex underlying mechanisms of neurodegenerative disorders including Alzheimer's disease (AD). The gut microbiota modulates gut brain axis by facilitating development of hypothalamic-pituitary-adrenal axis and synthesis of neuromodulators. The study was designed to unravel the effect of combined consumption of probiotics; Lactobacillus rhamnosus GG (LGG®) and Bifidobacterium BB-12 (BB-12®) (1 × 109 CFU) on AlCl3-induced AD mouse model in comparison with potent acetylcholine esterase inhibitor drug for AD, donepezil. Mice were randomly allocated to six different study groups (n = 8). Behavioral tests were conducted to assess effect of AlCl3 (300 mg/kg) and probiotics treatment on cognition and anxiety through Morris Water Maze (MWM), Novel Object Recognition (NOR), Elevated Plus Maze (EPM), and Y-maze. The results indicated that the combined probiotic treatment significantly (p < 0.0001) reduced anxiety-like behavior post AlCl3 exposure. The AlCl3 + LGG® and BB-12®-treated group showed significantly improved spatial (p < 0.0001) and recognition memory (p < 0.0001) in comparison to AlCl3-treated group. The expression status of inflammatory cytokines (TNF-α and IL-1ß) was also normalized upon treatment with LGG® and BB-12® post AlCl3 exposure. Our findings indicated that the probiotics LGG® and BB-12® have strong potential to overcome neuroinflammatory imbalance, cognitive deficits and anxiety-like behavior, therefore can be considered as a combination therapy for AD through modulation of gut brain axis. KEY POINTS: • Bifidobacterium BB-12 and Lactobacillus rhamnosus GG were fed to AlCl3-induced Alzheimer's disease mice. • This combination of probiotics had remarkable ameliorating effects on anxiety, neuroinflammation and cognitive deficits. • These effects may suggest that combined consumption of these probiotics instigate potential mitigation of AD associated consequences through gut brain axis modulation.

A quantitative meta-analysis of vitamin C in the pathophysiology of Alzheimer's disease.

Purpose: Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder with many complex pathways feeding into its pathogenesis and progression. Vitamin C, an essential dietary antioxidant, is vital for proper neurological development and maintenance. This meta-analysis and systematic review attempted to define the relationship between vitamin C plasma levels and AD while highlighting the importance and involvement of vitamin C in the pathogenesis of AD. Materials and methods: PRISMA guidelines were used to obtain studies quantifying the plasma levels of vitamin C in AD and control subjects. The literature was searched in the online databases PubMed, Google Scholar, and Web of Science. A total of 12 studies were included (n = 1,100) and analyzed using Comprehensive Meta-Analysis 3.0. Results: The results show that there is a significant decrease in the plasma vitamin C levels of AD patients as compared to healthy controls (pooled SMD with random-effect model: -1.164, with 95%CI: -1.720 to -0.608, Z = -4.102, p = 0.00) with significant heterogeneity (I 2 = 93.218). The sensitivity analysis showed directionally similar results. Egger's regression test (p = 0.11) and visual inspection of the funnel plot showed no publication bias. Conclusion: Based on these studies, it can be deduced that the deficiency of vitamin C is involved in disease progression and supplementation is a plausible preventive and treatment strategy. However, clinical studies are warranted to elucidate its exact mechanistic role in AD pathophysiology and prevention.