Scientists discover genetic mutation that may reduce Alzheimer’s risk: ScienceAlert

Researchers have discovered the biological workings of mutations in immune cells previously associated with Alzheimer’s illness. One of the mutations appears to play a protective role in the brain.

With tens of millions of people living with dementia around the world and limited means of treatment, decades and billions of dollars have been invested in studying the disease. Yet it still remains stubbornly mysterious.

So Stanford University neuroscientist Andy Tsai and colleagues tested different variations of the phospholipase C-gamma-2 (PLCG2) gene in mice to confirm and track the mechanism behind its previously identified association with Alzheimer’s.

This gene is known to be expressed in the brain microglia immune cells. These cells identify and devour invaders or other cells that have gone wrong in our brains.

PLCG2 is involved in signaling between microglia and inducing an inflammatory response, and is triggered when microglia encounter amyloid brain plaquesa common feature of Alzheimer’s disease.

“The microglial response affects neurons, which affects their ability to learn and form new memories,” explains Indiana University biochemist Gary Landreth.

When Tsai and his team eliminated the gene entirely, the mice became more likely to develop Alzheimer’s disease.

Microglia with PLCG2 mutations appear to respond differently to amyloid plaques, the researchers noted. They alter the ability of immune cells to alter and compact plaques.

One variation, M28L, acted just like the knockout – leaving the microglia unable to properly perform their task.

“They cannot efficiently mobilize a robust response to deposited amyloid,” the team writes. in your role.

But another version of the gene, P522R, was able to support the working memory of mice deficient in an Alzheimer’s disease model with increased activity of the PLCG2 protein.

Tsai and colleagues suspect that by allowing microglia to shrink plaques more effectively, the mutation helps clear the way for neurotransmitters to reach their targets in the brains of mice with features similar to Alzheimer’s disease.

This theory requires further testing to confirm, and although the protective mutation has been observed in humans, there is no data beyond a genetic association between M28L and Alzheimer’s in humans, as this mutation appears to be rare. But the new study aligns with recent suggestions that Alzheimer’s disease is an immune disease and amyloid plaques themselves are not what is malfunctioning.

Overall, the results indicate “that promoting a neuroprotective microglial response to amyloid pathology could limit the progression of Alheimer’s disease,” Tsai and team said. conclude.

This research was published in Immunity.

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