Alzheimer's Ignites a Neuron-Killing 'Forest Fire'

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We all know the devastating impact of Alzheimer's, the way it robs us of the person we once knew. In a recent post in Scientific American, Karen Weintraub explored some of the latest research findings in an article tittled "For Alzheimer’s Sufferers, Brain Inflammation Ignites a Neuron-Killing 'Forest Fire.'" Here is an excerpt, with a link to the full article at the bottom of the page.

For decades researchers have focused their attacks against Alzheimer’s on two proteins, amyloid beta and tau. Their buildup in the brain often serves as a defining indicator of the disease. Get rid of the amyloid and tau, and patients should do better, the thinking goes.

But drug trial after drug trial has failed to improve patients’ memory, agitation and anxiety. One trial of a drug that removes amyloid even seemed to make some patients worse. The failures suggest researchers were missing something. A series of observations and recently published research findings have hinted at a somewhat different path for progression of Alzheimer’s, offering new ways to attack a disease that robs memories and devastates the lives of 5.7 million Americans and their families.

One clue hinting at the need to look further afield was a close inspection of the 1918 worldwide flu pandemic, which left survivors with a higher chance of later developing Alzheimer’s or Parkinson’s. A second inkling came from the discovery that the amyloid of Alzheimer’s and the alpha-synuclein protein that characterizes Parkinson’s are antimicrobials, which help the immune system fight off invaders. The third piece of evidence was the finding in recent years, as more genes involved in Alzheimer’s have been identified, that traces nearly all of them to the immune system. Finally, neuroscientists have paid attention to cells that had been seen as ancillary—“helper” or “nursemaid” cells. They have come to recognize these brain cells, called microglia and astrocytes, play a central role in brain function—and one intimately related to the immune system.

All of these hints are pointing toward the conclusion that both Alzheimer’s and Parkinson’s may be the results of neuroinflammation—in which the brain’s immune system has gotten out of whack. “The accumulating evidence that inflammation is a driver of this disease is enormous,” says Paul Morgan, a professor of immunology and a member of the Systems Immunity Research Institute at Cardiff University in Wales. “It makes very good biological sense.”

The exact process remains unclear. In some cases the spark that starts the disease process might be some kind of insult—perhaps a passing virus, gut microbe or long-dormant infection. Or maybe in some people, simply getting older—adding some pounds or suffering too much stress could trigger inflammation that starts a cascade of harmful events.

This theory also would explain one of the biggest mysteries about Alzheimer’s: why some people can have brains clogged with amyloid plaques and tau tangles and still think and behave perfectly normally. “What made those people resilient was lack of neuroinflammation,” says Rudolph Tanzi, a professor of neurology at Harvard Medical School and one of the leaders behind this new view of Alzheimer’s. Their immune systems kept functioning normally, so although the spark was lit, the forest fire never took off, he says. In Tanzi’s fire analogy, the infection or insult sparks the amyloid match, triggering a brush fire. As amyloid and tau accumulate, they start interfering with the brain’s activities and killing neurons, leading to a raging inflammatory state that impairs memory and other cognitive capacities. The implication, he says, is that it is not enough to just treat the amyloid plaques, as most previous drug trials have done. “If you try to just treat plaques in those people, it’s like trying to put out forest fire by blowing out a match.”

Continue reading to find out more about 'Lighting the Fire,' 'Like Threads,' and 'Coming Soon?'

Karen Weintraub is a staff writer at USA Today, where she covers COVID, vaccine development and other health issues.