Gut Microbiota and Alzheimer’s Disease Pathogenesis
Introduction: Alzheimer’s Disease (AD) is the most common form of dementia affecting the elderly.1 AD is characterized by amyloid-beta (Aβ) plaques and tau protein neurofibrillary tangles in the brain. The brain forms lesions with the Aβ plaques and tau tangles, leading to synaptic damage and neuronal cell death primarily in the hippocampal region.1 This causes the classic AD symptoms of cognitive decline and memory impairment. AD is also characterized by changes in inflammation signaling, leading to the activation of microglia and astrocytes.2 The gut microbiome is the numerous and diverse population of micro-organisms living in human intestines.3 The microbiome communicates with the central nervous system through the microbiota-gut-brain axis.4 85% of dementia patients have a different gut microbiota composition than that of the healthy population.4 Studies suggest that gut microbiota have an impact on the pathogenesis of Alzheimer’s.3 The gut microbiome composition in AD patients has been shown to affect the integrity of the epithelial barrier, and is correlated with chronic intestinal and systemic inflammation.2,5 Studies found that when AD was modeled in mice, fecal transplants from healthy mice to AD-model mice were effective in alleviating Aβ deposition, tau tangles, reactive gliosis, and memory impairment.2,6 These findings suggest fecal transplant as a potential new treatment for AD. Methods. Alzheimer’s disease pathology was simulated through a transgenic mice model. These transgenic mice formed Aβ plaques, neurofibrillary tangles, and reactive gliosis in their brains as well as cognitive deficits.2 To determine the level of cognitive impairment, behavioral tests were performed.2 Sequencing of fecal metagenomic DNA was performed to determine differences in the gut microbiota between mice. A selection of the AD mice received fecal transfer from the WT mice. These mice were provided fresh fecal samples from WT mice orally for 16 weeks and became frequent fecal transfer (FMT) mice.2 ELISA was performed to determine the level of Aβ plaques in the brain of the AD mice. Additionally, tissue slices were stained with fluorescent antibodies for imaging.2 Results. There was a difference in composition of the gut microbiome between AD-model mice and WT mice.2 The frequent fecal transfer from WT to AD-model mice decreased Aβ plaques, neurofibrillary tangles, glial reactivity, and cognitive impairment.2 Conclusions. Current AD treatments do not slow or reverse the progression disease. These results indicate that fecal transplants have the potential to slow the progression of AD, and therefore offer better treatment outcomes compared to current options.
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