February 1 Research Roundup: Alzheimer’s, Gum Disease and Gut Bacteria, New Understanding of Cholesterol, Pancreatic Cancer and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Links Between Alzheimer’s and Gum Disease
Researchers with the biopharma company Cortexyme published research in the journal Science Advances recently describing the role Porphyromonas gingivalis (Pg), a bacteria that causes Gingivitis, chronic gum disease, in Alzheimer’s disease.
“Infectious agents have been implicated in the development and progression of Alzheimer’s disease before, but the evidence of causation hasn’t been convincing,” stated Stephen Dominy, Cortexyme co-founder, chief scientific officer, and lead author of the study. “Now, for the first time, we have solid evidence connecting the intracellular, Gram-negative pathogen, Pg, and Alzheimer’s pathogenesis while also demonstrating the potential for a class of small molecule therapies to change the trajectory of disease.”
The team discovered Pg in the brain of Alzheimer’s patients. Then, in mouse models, oral Pg infection led to brain colonization, which led to increased production of amyloid beta, the proteins associated with Alzheimer’s. They also identified gingipains, the Pg’s toxic proteases, in the neurons of Alzheimer’s patients.
The team further correlated the gingipain levels with disease pathology linked to two markers: tau, a protein needed for normal neuronal function, and ubiquitin, a protein tag that marks damaged proteins for degradation and is found in both tau tangles—common in the later stages of Alzheimer’s—and amyloid beta. Gingipains were found to be neurotoxic in the brains and in cell cultures.
Link Between Dementia and Microbiome
In research very similar to the previous story, researchers with the National Center for Geriatrics and Gerontology in Japan presented research at the American Stroke Association’s International Stroke Conference 2019 in Honolulu describing a connection between gut flora and dementia. The research team evaluated 128 patients with and without dementia, studying their fecal samples. They identified differences in the gut microbiota in patients with memory disorder.
“Although this is an observational study and we assessed a small number of the patients, the odds ratio is certainly high suggesting that gut bacteria may be a target for the prevention of dementia,” stated Naoki Saji, study author and vice director of the Center for Comprehensive Care and Research on Memory Disorders at the NCGG in Japan.
They found that concentrations of ammonia, indole, skatole and phenol were higher in dementia patients than in patients without dementia. But levels of Bacteroides, which are common in healthy guts, were lower in dementia patients.
New Insights into Cholesterol Mechanisms
Scientists at the University of Warwick in the UK published research in the Journal of Lipid Research that describes the effects of inhibiting the production of the enzyme diacylglycerol acyltransferase 1 (DGAT1). The enzyme is found in the liver and associated with the production of Very Low-Density Lipoproteins (VLDL), which retain fat in the form of triglycerides, choesterylesters, and cholesterol.
The team, led by Victor Zammit, from Warwick Medical School, found that inhibiting DGAT1 in the liver decreased the size of VLDL particles by almost half and reduced their triglyceride content.
“VLDL particles themselves are not harmful but when they are depleted of triglyceride after they offload it to other tissues, they become Low-Density Lipoprotein which are the carriers of ‘bad’ cholesterol,” stated Zammit. “This is the cholesterol that is associated with heart disease as the LDL deposit it within the walls of arteries, resulting in arteriosclerosis which can result in blockage of the coronary arteries with an associated increased risk of heart attacks and strokes.”
Controlling Genetic Inheritance Using CRISPR
Biologists at the University of California, San Diego (UCSD) used CRISPR to engineer a DNA element in mice, which was then passed down to their offspring. In this case, they engineered an active genetic “CopyCat” DNA element into the Tyrosinase gene that controls fur color. The CopyCat element disrupted both copies of the gene in mice, resulting in mice with black fur instead of white fur. The results of their research were published in the journal Nature.
“Our motivation was to develop this as a tool for laboratory researchers to control the inheritance of multiple genes in mice,” stated Kimberly Cooper, assistant professor at UCSD. “With further development we think it will be possible to make animal models of complex human genetic diseases, like arthritis and cancer, that are not currently possible.”
The research worked in female mice during egg production, but not in sperm production in males. They speculate that this is related to the timing of male and female meiosis.
Tongue Microbiome Might be Used to Diagnose Early-Stage Pancreatic Cancer
Our microbiome—the bacteria, viruses and fungi that live in different parts of our body are increasingly being found to play a significant role in our health as well as in various diseases. Researchers at Zenjiang University in China published research in the Journal of Oral Microbiology describing how differences in bacteria living on the tongue may be able to diagnose early-stage pancreatic cancer.
“If an association between the discriminatory bacteria and pancreatic cancer is confirmed in larger studies, this could potentially lead to the development of new microbiome-based early diagnostic or preventive tools for the disease,” stated lead author Lanjuan Li.
The team evaluated the tongue microbiome of 30 patients with early-stage disease who had been diagnosed with a tumor positioned in the “head” area of the pancreas and a similar group of 25 healthy people. Everybody involved was between the ages of 45 and 65 years with no other diseases or oral health issues, nor had they taken antibiotics or other drugs in the three months before the study. They used gene sequencing to study the microbiome diversity of tongue coat samples. In the patients with pancreatic cancer, there was an abundance of four types of bacteria compared to the healthy group. Haemophilus and Porphyromonas appeared in low levels and Lepidotrichia and Fusobacteria appeared in high levels.
Autophagy Appears to Prevent Cancer from Starting
Autophagy is a cellular process, a sort of garbage disposal, that takes apart unnecessary or dysfunctional components, allowing them to degrade and be recycled. Researchers with the Salk Institute for Biological Studies in San Diego published research in the journal Nature that showed autophagy to be a novel tumor-suppressing pathway.
“These results were a complete surprise,” stated Jan Karlseder, a professor in Salk’s Molecular and Cell Biology Laboratory and the paper’s senior author. “There are many checkpoints that prevent cells from dividing out of control and becoming cancerous, but we didn’t expect autophagy to be one of them.”
As has been commonly understood and reported, telomeres, the ends of chromosomes, similar to the plastic tips at the end of shoelaces, shorten a little bit each time DNA divides. When telomeres become so short they no longer protect chromosomes, cells receive signals to stop dividing permanently. Sometimes viruses or other factors prevent that signal and cells keep dividing, but the cells and chromosomes are often dysfunctional—this is common in many cancers.
By preventing autophagy, the scientists found unexpected results—without autophagy, cells continued to replicate. The chromosomes were fused and abnormal. What this meant was that autophagy was an important early cancer-suppressing mechanism. Autophagy was believed to actually fuel cancer growth by cannibalizing other cells, but now it appears it is actually a preventive mechanism.