Gonorrhea could be the driver of gene mutations that fight against dementia, improving cognition

University of California San Diego researchers have successfully built off their previous research, uncovering human gene mutations that protect cognition in older adults. Now in their latest work, they focused on the evolution of one specific gene. Their findings suggest that selective pressure from pathogens like gonorrhea may have promoted the emergence of the gene variant, supporting older humans to live long enough to become grandparents.

Before, when they compared human and chimp genomes, they found that humans had a unique version of the gene for CD33, which is a receptor expressed in immune cells. The standard CD33 receptor binds to a sugar called sialic acid, which coats all human cells. When the immune cell senses the sialic acid via CD33, it recognizes the other cell as part of the body and doesn’t attack, which prevents an autoimmune response. Things get dicey when plaque formation begins, which is an early sign of Alzheimer’s disease and dementia. The sialic acid sugars can bind to the plaques and increases the risk of dementia even more.

The new gene variant builds off this premise. Throughout evolution, humans picked up an additional mutated form of CD33 that is missing the binding site for the sialic acid. The mutated receptor no longer reacts to sialic acids on damaged plaque. So without the binding, higher levels of this CD33 variant were found to be protective against late-onset Alzheimer’s.

Co-senior author Dr. Ajit Varki, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UCSD’s School of Medicine, and colleagues found strong evidence that suggests there is a driver pushing the variant to evolve quicker and more efficiently. They also discovered that this particular version of CD33 was not present in our closest genetic relatives, which are Neanderthals or Denisovans.

“For most genes that are different in humans and chimps, Neanderthals usually have the same version as the humans, so this was really surprising to us,” says Varki, in a statement. “These findings suggest the wisdom and care of healthy grandparents may have been an important evolutionary advantage that we had over other ancient hominin species.”

It’s possible that extremely infectious diseases may explain this. Diseases like gonorrhea can negatively impact reproductive health. Gonorrhea bacteria coat themselves in the same sialic acid sugars that CD33 receptors bind to, meaning that these molecules can appear the same as the normal ones, ultimately tricking the body. The team believes that the variant ultimately came about because of this “copying” of sorts. It had to beat out the harmful evolutionary outcome caused by different pathogens.

Ultimately, the team believes humans initially inherited the mutation to protect against gonorrhea during reproductive age, and the variant was later taken up by the brain to fight against dementia.

“It is possible that CD33 is one of many genes selected for their survival advantages against infectious pathogens early in life, but that are then secondarily selected for their protective effects against dementia and other aging-related diseases,” says Pascal Gagneux, PhD, professor of pathology at the school and professor in the Department of Anthropology.

More research is encouraged, expanding on this novel insight and enhancing therapeutic approaches for neurodegenerative diseases.

The study is published in the journal Molecular Biology and Evolution.

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About the Author

Shyla Cadogan

Shyla Cadogan is a recent graduate from the University of Maryland, College Park with a Bachelor’s of Science in Nutrition and Food Science. She is on her way to becoming a Registered Dietitian, with next steps being completion of a dietetic internship at the University of Maryland Medical Center. Shyla has extensive research experience in food composition analysis and food resource management.

Comments

  1. does that mean that if you have the “clap” early in life, you won’t get dementia later in life?
    whew! another bullet dodged!

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