Research Roundup: Gut Disorders Linked to Alzheimer’s, ASOs Target Cystic Fibrosis & More

Research Roundup: Gut Disorders Linked to Alzheimer’s, ASOs Target Cystic Fibrosis & More

Published: Jul 22, 2022

By Mark Terry

Alzheimer’s disease (AD) is not totally understood. The abnormal accumulation of proteins in the brain, such as beta-amyloid and tau, is involved with the disease, as is neuroinflammation. But other factors are also associated with this disease, including gut disorders. For that and more research news, continue reading.

A Link Between Gut Disorders and Alzheimer’s Disease

People with certain disorders of the gut may be at greater risk of developing Alzheimer’s disease, and a study from Edith Cowan University confirmed the association.

The latest research analyzed large genetic data sets from AD and several gut-disorder studies of approximately 400,000 people. Their analysis found that people with AD and gut disorders have genes in common. Although the study didn’t conclude that gut disorders cause AD or vice versa, they do support the concept of the so-called “gut-brain” axis, a two-way relationship between the brain’s cognitive and emotional centers and the functioning of the intestines. The research was published in the journal Communications Biology.

In addition, they found that abnormal cholesterol levels were a risk for both AD and gut disorders.

“Looking at the genetic and biological characteristics common to AD and these gut disorders suggests a strong role for lipids metabolism, the immune system, and cholesterol-lowering medications,” Emmanuel Adewuyi, Ph.D., research lead of the study, said. “Whilst further study is needed into the shared mechanisms between the conditions, there is evidence high cholesterol can transfer into the central nervous system, resulting in abnormal cholesterol metabolism in the brain. There is also evidence suggesting abnormal blood lipids may be caused or made worse by gut bacteria (H.pylori), all of which support the potential roles of abnormal lipids in AD and gut disorders. For example, elevated cholesterol in the brain has been linked to brain degeneration and subsequent cognitive impairment.”

The research also supports the theory that some cholesterol-lowering drugs, such as statins might be beneficial in treating both AD and gut disorders. More research is needed.

A New Approach to Treating Cystic Fibrosis

Researchers at Cold Spring Harbor Laboratory discovered how antisense oligonucleotides (ASOs) could create a protein missing in cystic fibrosis (CF) patients. ASOs are molecules that can be leveraged to control cellular protein levels. CF is caused by any one of hundreds of mutations in the gene that encodes for a protein called CFTR. The research group found a new way to use ASOs to make more of a functional, although not perfect, version of CFTR. The imperfect CFTR protein is caused by a gene mutation, which results in cells receiving the wrong instructions for making the CFTR protein. The mistaken instructions are eliminated, and the protein isn’t made. But what the research did was trick the cells into using the imperfect instructions and making the slightly abnormal CFTR protein. In CF, they found that an imperfect CFTR protein is better than none. This approach improved lung cell function.

A Better Understanding of How Melanoma Spreads in the Brain

Investigators with Columbia University Irving Medical Center completed what is believed to be one of the most comprehensive studies of the cells inside melanoma brain metastases. It’s not well understood why melanoma, a kind of skin cancer, spreads to the brain and generally has lower response rates to many treatments. The researchers invented new techniques for analyzing single-cell genetics of frozen brain samples, which allowed them to analyze tissue from patients who had not been treated. They analyzed the genes expressed in more than 100,000 individual cells. They found that melanoma brain metastases are more chromosomally unstable than melanoma metastases in other body parts. This, in turn, triggers signaling pathways that increase the likelihood of metastases and the ability of the cancer cells to suppress the immune system. They believe these newfound pathways could be potential targets for new therapies.

How Belly Fat Increases Risk of Metabolic Disease

Researchers with King’s College London studied data from TwinsUK to learn more about how belly fat increases the risk of metabolic disease. They leveraged samples from 538 participants that combined genetic, gene function, diet, and health data. Their particular focus was epigenetic markers. These are like molecular switches that turn genes on or off based on different environmental factors. One was a gene where the identified epigenetic changes were known to be a potential mechanism where diet affects belly fat accumulation. Others were epigenetic markers that have effects on metabolic health. They were able to develop an epigenetic predictor of insulin resistance associated with their findings of elevated belly fat. After controlling for BMI, the SAT methylome showed a distinct epigenetic signature linked with visceral fat.

Booster Shots Help Battle Omicron

The Omicron subvariants of COVID-19 are particularly adept at evading immunity caused by previous infection and vaccines. However, a new study out of the University of Washington School of Medicine/UW Medicine evaluated a panel of vaccines available in the U.S. and globally and found that booster shots offset some of these variants’ immune evasion tactics. The research supported earlier evidence that a third vaccine dose expands existing memory B cells specific to the viral spike protein as well as stimulating new memory B cells. This causes the production of antibodies with enhanced potency against the Omicron subvariants. Their research also showed that the Omicron BA.5, which along with BA.4, is now the dominant strain globally, has an ability to bind with its host ACE2 receptor that is six times stronger than the ancestral SARS-CoV-2 (Wuhan) strain. However, they’re all slower at the next step, fusing with the membrane on the host cell. They evaluated vaccines produced by Moderna, Pfizer-BioNTech, Novavax, Janssen (J&J), AstraZeneca, Sinopharm and Sputnik V.

The authors wrote, “The marked improvement in plasma neutralizing activity for subjects that received a booster dose over those that did not highlights the importance of vaccine boosters for eliciting potent neutralizing antibody responses against Omicron sublineages.”

Source: BioSpace