There is mounting evidence that the underlying mechanisms of Alzheimer’s disease may begin years, if not decades, before symptoms appear. Many researchers believe that treating those affected as soon as possible will be the most effective way of slowing or stopping the disease’s progression.
Mice genetically modified to prevent the production of a specific type of immune cell struggled to form new memories. Could a lack of immune cells that are poorly understood contribute to Alzheimer’s disease and other forms of cognitive decline? According to a Rutgers study published in Nature Immunology, it could, and increasing these cells could reverse the damage.
Researchers from Rutgers University deactivated the gene that produces mucosal-associated invariant T cells (MAITs) in mice and compared cognitive function in normal and MAIT cell-deficient mice. The two groups performed similarly at first, but as the mice reached middle age, the genetically altered mice struggled to form new memories.
When the researchers injected MAITs into the genetically altered mice, their performance in learning and memory-intensive tasks like swimming through a water maze returned to normal.
MAIT cell production is linked to bacteria in your gut microbiome. People who grew up in relatively sterile environments or who took antibiotics frequently produce fewer of them than those who grew up in more rural areas, where beneficial bacteria are more prevalent. However, anyone can improve their microbiota by changing their diet or living environment.
Qi Yang
The authors of the study believe this is the first study to link MAITs to cognitive function and hope to follow up with research comparing MAIT numbers in healthy humans and those with cognitive diseases such as Alzheimer’s.
“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 allow us to compare levels in healthy subjects and those with Alzheimer’s disease and other cognitive disorders,” said Qi Yang, senior author of the study and associate professor at Rutgers Robert Wood Johnson Medical School’s Child Health Institute of New Jersey.
MAIT cells, which were discovered in the 1990s, were already known to be the most abundant innate-like T cells in humans and to be particularly numerous in the liver and skin. The Rutgers study was the first to detect these cells, which are not fully understood when it comes to fighting disease, in the meninges, the membrane layers that cover the brain.
MAITs found in the meninges appear to protect against cognitive decline by producing antioxidant molecules that fight toxic byproducts of energy production known as reactive oxidative species. In the absence of MAITs, reactive oxidative species accumulate in the meninges, causing meningeal barrier leakage. When the meningeal barrier breaches, potentially toxic substances enter the brain and cause inflammation. This buildup eventually interferes with brain and cognitive function.
Many researchers believe that the habit of staying mentally active as you age is more important than education level in maintaining a healthy brain. In one study, people in their 70s and 80s who were mentally intact were asked how often they did six activities that required active mental engagement: reading, writing, doing crossword puzzles, playing board or card games, participating in group discussions, and playing music.
Genetic alteration prevented the experimental mice from producing any MAIT cells, but humans can probably increase MAIT cell production by altering their diets or making other lifestyle changes, said Yuanyue Zhang, the lead author of the study and a postdoctoral researcher at the Child Health Institute of New Jersey.
“MAIT cell production is linked to bacteria in your gut microbiome,” Zhang explained. “People who grew up in relatively sterile environments or who took antibiotics frequently produce fewer of them than those who grew up in more rural areas, where beneficial bacteria are more prevalent. However, anyone can improve their microbiota by changing their diet or living environment. This is yet another reason to live a natural and healthy lifestyle.”
