The Science & Technology desk gathers a weekly digest with impactful and interesting research publications and developments at Stanford. Read the latest in this week’s Research Roundup.

Reducing the risk of dementia

Dementia is the gradual diminishing of memory over time. While researchers have tried to produce effective treatments for diseases that cause dementia like Alzheimer’s, many efforts have been unsuccessful. As a result, some researchers tried to tackle this issue through another way: the Shingles vaccine. 

Shingles is a reactivated virus from the dormant virus in people previously diagnosed with chickenpox. A Stanford-led study published in Nature found that recipients of the shingles vaccine have a lower risk of developing dementia compared to others who do not take the vaccine. 

Over a seven year timespan, researchers tracked health outcomes in two groups of the study population: those who received the vaccine and those who did not. 

While it was not a surprise that researchers found the Shingles vaccine to lower the amount of Shingles occurrence in the population, what was consequential was that they also found that people who took the Shingles vaccine were, according to Stanford Medicine, “20% less likely to develop dementia than the unvaccinated.” 

Findings from the study also suggested that women had a stronger response to protection against dementia than males; researchers hypothesize that this could be due to a stronger antibody production from women in response to the vaccine. 

How exactly the vaccine protects against dementia on a molecular level – whether through a specific mechanism or augmenting the immune system’s response – is still in question. 

Pascal Geldsetzer, a senior author of the study and assistant professor of psychiatry and behavioral sciences, highlighted the significance of the results from this study.

“We just keep seeing this strong protective signal for dementia in dataset after dataset,” he told Stanford Medicine. 

A new, potential avenue of arterial development

Our arteries are responsible for delivering oxygenated blood throughout the heart. However, in conditions such as atherosclerosis, arteries can develop a buildup of triglycerides and cholesterol, blocking the oxygenated blood from reaching the heart. Over time, this buildup can lead to coronary artery disease and increases the individual’s risk of a heart attack. 

Sanford researchers have now found a gene – CXCL12 – that is responsible for the formation of the posterior descending artery, as described in their study published in Cell. They are hopeful that this can provide a viable option to compensate for the lack of proper function of other blocked arteries.

Through genetic analysis from a database with health information of veterans through the Million Veteran Program, researchers were able to examine the connections between human DNA and the development of this artery, with the location of highest significance being CXCL12. 

While previous research had found that increasing the amount of protein associated with CXCL12 increased arterial formation in mice, this study was able to emphasize the gene’s relationship with arterial development in humans, a major stepping stone for potential development of new arterial branches. 

Kristy Red-Horse, a senior author of the study and professor of biology, emphasized the significance of the finding.

“For the first time, we have evidence of a gene that regulates the development of one of the most important types of arteries in the human body,” Red-Horse told Stanford Report. 

Not just for energy – how glucose helps drive differentiation

A Stanford-led study published in Cell revealed the glucose molecule to be a master regulator of tissue differentiation, which controls the expression of other genes throughout this process. 

Previously, the researchers had hypothesized that molecules that proliferate throughout differentiation may be more likely to hold an influential role in the process. However, after testing this hypothesis through mass spectrometry and various screening methods, they found glucose to be one of the molecules that drastically increased in abundance. This was unexpected, as glucose is typically known as solely a molecule for energy. The researchers confirmed this through using fluorescence—  cells increased in fluorescent intensity as the differentiation process continued, reflecting higher glucose levels. 

When the researchers attempted to differentiate skin organoids with lower-than-normal glucose levels, the organoids did not differentiate properly, as multiple other genes had also been affected by the lack of glucose. When the organoids were placed in a solution containing glucose, differentiation was successful.

Researchers discovered a previously unknown mechanism behind glucose’s strong role in differentiation; when glucose enters a cell, it binds to many proteins, notably IRF6, which undergoes a conformational change and stimulates a myriad of other genes that play a role in differentiation. 

Paul Khavari, a senior author of the study and chair of dermatology, articulated the significance of this new understanding of glucose.

“This is an entirely new and growing field,” Khavari told Stanford Medicine. “People have thought that small biomolecules like glucose were quite passive in the cell.”