A Twisted Tale of Genes, Microbes, and Alzheimer's, Part 1
Bacteria are associated with a gene for Alzheimer's. Can we control them?
“The mystery of what goes on inside the mind of another person becomes terrifyingly impenetrable in the final stages of dementia; twilight to pitch dark at the vanishing line between life and death.” ― Nicci Gerrard
According to the World Health Organization, Alzheimer's is one of our most debilitating diseases. It effectively erases who you are, insinuating itself at first with annoyance, then anger, then fright, and finally silence. It can take 20 years to play out, exhausting caregivers, family, and friends. As the population ages, we can expect a precipitous rise in the number of Alzheimer's patients. But a new study provides hope that we may be able to mitigate this onslaught with diet.
How Alzheimer's takes over the mind is still hotly debated, but we know one thing: There is a gene that increases your odds of getting the disease. It is called APOE4, and it creates a subtly defective version of a protein that normally helps chaperone fats around the body. One of the organs that uses a lot of fat is the brain, where it plays a major role in membrane structure and providing energy. But just how APOE4 might contribute to Alzheimer's is still murky.
New Study
So, a new study from the University of Nevada is an eye-opener. Jingchun Chen and colleagues found a connection between gut microbes, Alzheimer’s, and the APOE4 gene. They identified 10 gut microbial genera associated with Alzheimer’s, with six showing a protective association and four showing a risk association.
The protective bacteria included Eubacterium nodatum, Eisenbergiella, Eubacterium fissicatena, Actinobacterium adlercreutzia, Actinobacterium gordonibacter, and Prevotella. The risk-associated bacteria included Collinsella, Lachnospira, Bacteroides, and Veillonella. Don’t worry about these crazy names, there will not be a test on them. But they are here should you need them.
Veillonella has previously been associated with oral infections in Alzheimer’s patients. Porphyromonas gingivalis is another oral microbe associated with Alzheimer's, and highlights the role of oral bacteria, not just gut bacteria, in dementia.
The association these researchers found between these microbes and Alzheimer’s was independent of age and sex. Further analysis revealed a correlation between the APOE4 gene and four of the bacteria. One of those was Collinsella. Collinsella has been previously associated with atherosclerosis, rheumatoid arthritis, and type-2 diabetes. Studies have shown that Collinsella exhibits pro-inflammatory effects and affects lipid metabolism, which suggests a functional relationship to APOE4.
Additionally, three bacteria were found to have a protective association with APOE4. These bacteria are involved in the production of butyrate, which has anti-inflammatory properties and helps to maintain gut integrity. Butyrate also affects the brain directly, improving its ability to adapt to challenges and to regenerate brain tissue.
The gut-brain axis
We have known for several years now that gut microbes have an important impact on the brain. They can produce both nasty toxins and healthy short-chain fatty acids like butyrate. A diverse and well-balanced community of microbes can keep your gut lining pink and happy, welcoming nutrients while expelling pathogens. But the researchers found that a reduction in microbial diversity was associated with the development of Alzheimer's. Other studies have shown that a healthy gut is typically the most diverse gut.
When certain species of bacteria are wiped out, say by antibiotics, pathogens, or a bad diet, other bully species can take over. That can cause the gut lining to weaken, potentially allowing microbes or toxins to enter the bloodstream. Over time, that can lead to systemic inflammation, which can affect every organ in the body, including the brain. So, on the face of it, it doesn’t sound crazy that bacterial imbalances could lead to Alzheimer’s.
Next week, we will look harder at causality, and discuss what this research can tell us about diet and other ways to stave off this terrible disease. If you aren’t already subscribed, click the button below so you don’t miss the end of the story. Don’t forget to share this article with friends and loved ones who are affected by Alzheimer's – it’s not often that we hear good news about this subject.
References
Cammann, D., Lu, Y., Cummings, M.J. et al. Genetic correlations between Alzheimer’s disease and gut microbiome genera. Sci Rep 13, 5258 (2023).