Figuring out how immune cells prevent cognitive decline

Could Alzheimer’s disease and other types of cognitive decline be caused by the underproduction of immune cells that are poorly understood? It might, according to a Rutgers study published in Nature Immunology, and increasing these cells could undo the harm.


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Researchers from Rutgers University deactivated the gene in mice that make mucosal-associated invariant T cells (MAITs), and then they assessed the cognitive abilities of mice with and without MAIT cell deficiency.

The two groups of mice performed equally at first, but as they reached middle age, the genetically altered mice had trouble creating new memories.

When the genetically modified mice were given MAIT injections, their performance on learning- and memory-demanding tasks, like swimming through a water maze, returned to normal.

The researchers hope to expand on this work by comparing the numbers of MAITs in healthy humans and those who have cognitive diseases like Alzheimer’s. They believe that this is the first study to link MAITs to cognitive function.

The MAIT cells that protect the brain are located in the meninges, but they are also present in blood, so a simple blood test should let us compare levels in healthy subjects and those with Alzheimer’s disease and other cognitive disorders.

Qi Yang, MD, PhD, Study Senior Author and Associate Professor, Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University

Prior to their discovery in the 1990s, MAIT cells were already known to be the most prevalent innate-like T cells in humans and to be particularly prevalent in the skin and liver. In the meninges, the membrane layers that cover the brain, the Rutgers study was the first to identify these cells, whose role in disease resistance is not fully understood.

By producing antioxidant molecules to combat reactive oxidative species, toxic byproducts of energy production, MAITs nested in the meninges appear to guard against cognitive decline. Without MAITs, reactive oxidative species build up in the meninges and result in leakage of the meningeal barrier.

Potentially toxic substances enter through a meningeal barrier leak, inflaming the brain. This buildup eventually impairs cognitive and brain function.

According to Yuanyue Zhang, the study’s lead author and a postdoctoral researcher at the Child Health Institute of New Jersey, genetic modification prevented the experimental mice from producing any MAIT cells, but humans can likely increase MAIT cell production by changing their diets or other lifestyle choices.

MAIT cell production is connected to the bacteria in your gut microbiome. People who grew up in relatively sterile environments or took antibiotics frequently make fewer of them than people who grew up in more rural areas, where there is more exposure to beneficial bacteria. But everyone may improve their microbiota by changing their diet or living environment. This is just one more reason to pursue a natural and healthy lifestyle.

Yuanyue Zhang, Study Lead Author and Postdoctoral Researcher, Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University

Journal reference:

Zhang, Y., et al. (2022). Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function. Nature Immunology.


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