Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

A Mouse Model of Alzheimer's Disease with Transplanted Stem-Cell-Derived Human Neurons

Alzheimer’s disease（AD）,the main cause of dementia,is defined by the combined presence of amyloid-b（Ab）deposition and abnormal tau aggregation[1].Experimental models are critical to obtain a better understanding of AD pathogenesis,and to evaluate the potential of novel therapeutic approaches.The most commonly used AD

Using Huntingtin Knock-In Minipigs to Fill the Gap Between Mouse Models and Patients with Huntington's Disease

Huntington＇s disease （HD） is an inherited autosomal dominant neurodegenerative disease characterized by pro- gressive motor deficits, cognitive decline, and psychiatric symptoms. It is caused by a pathological expansion of CAG trinucleotide repeats in exon 1 of the HD gene, resulting in the translation of a mutant form of huntingtin protein （mutant Htt） with an expanded polyglutamine domain in the N-terminal region [1 ]. Despite great progress in understanding the pathogenesis of HD using multiple mouse models, the exact mechanisms by which mutant Htt induces neuronal dysfunction and death are still not completely clear, and there is no curative treatment for this disease. An important reason is that the mouse, which is the most widely used animal model in HD research, differs from the human in many aspects, including the physiology, drug metabolism, blood-brain barrier, life span, brain volume, and neuroanatomical organization [2]. Thus, it is necessary to establish HD models with higher species than rodents, such as the dog, pig, and non- human primate, so as to bridge the gap between preclinical mouse models and clinical studies.