Microglia, specialized cells like the one in the center of this image, can help prevent Alzheimer's disease. Researchers say that the cells can contribute to the progression of the illness.
Juan Gaertner/Science SourceGenetic data was the beginning of it all.
There is a gene here.
If scientists can find a cure for Alzheimer's disease, they should look to the immune system.
Many genes involved in various immune system functions have been identified that may contribute to Alzheimer's.
The focus of intense research is on genes that control little immune cells called microglia, which are believed to be the cause of Alzheimer's.
Microglia are brain cells that protect the brain from injuries and invaders. They help clear dead or impaired brain cells. We would be in trouble without them.
The immune system of the brain clears away aamyloid as junk.
Sometimes it builds up. The toxic accumulation is caused by certain genes. Impaired microglial function is one of the possible consequences of traumatic brain injury.
Everyone agrees that there is too much amyloid in the brain of people with Alzheimer's.
When amyloid starts to accumulate in the brain cells, it causes the formation of a new protein called tau. Many experts believe that the inflammatory immune response that is caused by the presence of tau can lead to brain damage in Alzheimer's.
Several genes involved in immune and microglial function have been linked to Alzheimer's.
CD33 was identified in 2008.
When we got the results, I ran to my colleague's office next door and told him to see it.
Rudy, who goes by Tanzi, led the research. Time magazine named the discovery a top medical breakthrough of 2008.
He jokes that they were laughing because they had no idea what this gene did.
Tanzi and his group discovered that CD33 is a kind of microglial on-off switch, which causes the cells to become inflammatory.
When it came to the genetics, he says, we kind of got it all going.
Microglia are known to recognize unwanted patterns associated with microbes and cellular damage. They know how to eat dead tissue and unfamiliar pathogens. Tanzi believes that the brain damage caused by an infection can cause the microglia to become hyper.
He explains that the modern human immune system evolved hundreds of thousands of years ago. The majority of people didn't live long enough to develop dementia or the withered brain cells that comes with it, and our lifespans at the time were far shorter than they are today. Our immune system assumes that any faulty brain tissue is due to a microbe. Microglia clear the area to prevent the spread of infections.
Even if it isn't, they say we better wipe out this part of the brain. Tanzi says that they don't know what causes inflammation. This response is turned on by CD33 The microglia become killers, not just janitors.
CD33 is the Yin and TREM2 is the yang.
TREM2 was discovered a few years after CD33 and returned to their role as cellular housekeepers.
David Holtzman, a neuroscience researcher at Washington University in St. Louis, agrees that where you find dead brain cells, there are microglia.
He says that a lot of people thought that the cells were reacting to Alzheimer's pathology and not necessarily a cause of the disease.
It was the discovery of TREM2 on the heels of CD33 that really shifted the thinking, in part because it produces a protein that is only found in the brain. The genes that run our bodies and brains are found in stretches of DNA.
Many of us in the field immediately said, "Look, there is now a risk factor that is only expressed in microglia." It must be that innate immune cells are important in the pathogenesis of the disease.
The double-edged sword is the activation of the microglial cells. microglia clear amyloid to maintain brain health. Inflammation that comes from microglial activation is more harmful than good once amyloid andtau have done enough damage. Alzheimer's sets in.
Some researchers are not convinced.
Serge Revist is a professor at the medical school in Quebec. He believes that the root cause of Alzheimer's is not the immune cells.
He believes that the excess amyloid in some Alzheimer's patients may not be able to be handled by the immune system, and that developing treatments that improve the ability of the immune system to clear it could be effective.
The cascade of events leading to Alzheimer's is complicated.
The amyloid is likely to be a major contributor. Immune activity caused by early life infections may be involved in some cases. The infectious theory of Alzheimer's was first proposed by Robert Moir. Tanzi's group has evidence that amyloid evolved to protect us from pathogens only to become a problem when it becomes too much.
The same goes for microglia, cells that may cause Alzheimer's.
Doctors might one day be able to slow or even stop the progression of dementia if a treatment could decrease CD33 activity or increase TREM2. A therapy that quells the immune response to amyloid might be the answer to treating dementia.
There are many scientists and companies trying to figure out how to influence genes like TREM2 and CD33, and to decrease amyloid and act on the downstream consequences of the protein.
The most common form of dementia may be due to a well-intentioned immune cell going rogue.
Tanzi says you would hear this from any researcher worth their salt.
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