R&I – FS
It all started with genetic data.
A gene here, a gene there.
Eventually the story became clearer: If scientists are to one day find a cure for Alzheimer’s disease, they should look to the immune system.
Over the past couple decades, researchers have identified numerous genes involved in various immune system functions that may also contribute to Alzheimer’s.
Some of the prime suspects are genes that control humble little immune cells called microglia, now the focus of intense research in developing new Alzheimer’s drugs.
Microglia are amoeba-like cells that scour the brain for injuries and invaders. They help clear dead or impaired brain cells and literally gobble up invading microbes. Without them, we’d be in trouble.
In a normal brain, a protein called beta-amyloid is cleared away through our lymphatic system by microglia as molecular junk.
But sometimes it builds up. Certain gene mutations are one culprit in this toxic accumulation. Traumatic brain injury is another, and, perhaps, impaired microglial function.
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Holtzman sees microglial activation in impending dementia as a double-edged sword. In the beginning, microglia clear unwanted amyloid to maintain brain health. But once accumulated amyloid and tau have done enough damage, the neuroinflammation that comes with microglial activation does more harm than good. Neurons die en masse and dementia sets in.
Not all researchers are convinced.
Serge Revist is a professor in the Department of Molecular Medicine at the Laval University Medical School in Quebec. Based on his lab’s research, he believes that while impaired immune activity is involved in Alzheimer’s, it’s not the root cause. “I don’t think it’s the immune cells that do the damage, I still think it’s the beta-amyloid itself,” he says, “In my lab, in mouse studies, we’ve never found that immune cells were directly responsible for killing neurons.”
He does believe that in some Alzheimer’s patients microglia may not be able to handle the excess amyloid that accumulates in the disease, and that developing treatments that improve the ability of microglia and the immune system to clear the protein could be effective.
FoundingFrog