Alzheimer's disease
Alzheimer’s disease is a progressive neurodegenerative disorder that slowly destroys memory and thinking and is the most common form of dementia. Alzheimer’s disease is characterized by amyloid beta plaques and neurofibrillary tangles in the brain along with both inflammation in the brain and systemically. This has led to a prominent theory that microbial communities or pathogenic infections are causative in the development of the inflammation seen in this disease that leads to pathological findings and cognitive decline. Our group has recently published findings among a cohort of nursing home elders demonstrating a dysbiotic pattern seen when comparing older adults with Alzheimer’s disease to those with no dementia. This is hallmarked by a reduction in the proportion and prevalence of bacteria with the potential to synthesize butyrate, an essential metabolite in the human colon with anti-inflammatory properties, as well as an acquisition of taxa that are known to cause pro-inflammatory states.
Thus, a nexus between the intestinal microbiome, systemic inflammation, immune phenotypic changes and AD could be a means by which the microbiome can impact this devastating neurodegenerative disorder.
The main goal of our current NIH-NIA (https://grantome.com/grant/NIH/RF1-AG067483-01) funded project which is also funded by the Alzhiemer's Association (https://www.alz.org/research/for_researchers/grants/funded-studies-details?FundedStudyID=2280) is to transition our microbiome association studies with Alzheimer’s disease more towards causality by investigating how the Alzheimer’s disease microbiome dysbiosis observed correlates with inflammation and immunosenescence in different groups or older adults and how this ultimately leads to cognitive decline. We also propose to reveal how Alzheimer’s disease microbiome dysbiosis can affect intestinal epithelial homeostasis and microglial functionality in several of our in vivo/vitro model systems. These objectives underscore our central hypothesis that there is a characteristic dysbiotic microbiome among AD elders, regardless of living environment, and that the level of inflammation-type dysbiosis positively correlates with both local and systemic inflammation and eventually cognitive decline.