Increased expression of SLC25A18 is associated with Alzheimer's disease and is involved in Aß42-induced mitochondrial dysfunction and apoptosis in neuronal cells.

Alzheimer's disease (AD) is currently one of the most serious public health concerns in the world. However, the best approach to treat AD has yet to be discovered, implying that we must continue to work hard to find new AD target genes. In this study, we further analysed Gene Expression Omnibus (GEO) data and discovered that the expression of the Mitochondria glutamate carrier SLC25A18 is associated with AD by screening the differentially expressed genes in different regions of the brains of Alzheimer's disease patients. To verify the expression of SLC25A18 during Alzheimer's disease development, we analysed animal models (5×FAD transgenic AD animal model, chemically induced AD animal model, natural ageing animal model), and the results showed that the expression of SLC25A18 was increased in animal models of AD. Further investigation of the different regions found that SLC25A18 expression was elevated in the EC, TeA, and CA3, and expressed in neurons. Next, We found that Aß42 treatment elevated SLC25A18 expression in Neuro 2A cells. Reducing SLC25A18 expression attenuated mitochondrial dysfunction and neuronal apoptosis caused by Aß42. Overexpression of SLC25A18 increased ATP and intracellular superoxide anions but decreased mitochondrial membrane potential. The results indicate that SLC25A18 affects mitochondrial function and neuronal apoptosis, and is related to AD, which makes it a potential target for treating brain dysfunction.

The relationship between Alzheimer's disease and intestinal microflora structure and inflammatory factors.

To analyze the structural characteristics of intestinal microflora and changes of serum inflammatory factors of the Alzheimer's disease, and to explore the relationship between them and dementia, we selected 30 patients in the AD group and 30 patients in the normal group, and collected stool samples to analyze the intestinal flora structure characteristics of the two groups of patients, and statistically analyzed the inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-8 by ELISA from the venous blood of the two groups. The results show that the dominant Bacteroides in the two groups are Bacteroides, Firmicutes, Proteobacteria, and Actinobacteria. The abundance of Bacteroides, Firmicutes, and Proteobacteria in the AD group shows a statistical difference. At the genus level, the abundance of anti-inflammatory bacteria such as Lactobacillus, Bifidobacterium, and Ruminococcus drops in AD group, while the abundance of pro-inflammatory bacteria such as Escherichia and Enterococcus raises. Statistical analysis of inflammatory cytokines in the two groups suggests that TNF-α and IL-6 levels significantly increase in the AD group, with statistical differences. Therefore, it is speculated that the increased abundance of pro-inflammatory bacteria in intestinal flora may lead to or aggravate neuroinflammation through the release of inflammatory factors, thus further leading to the occurrence and development of AD.