Saturday, March 21, 2015

Alzheimer's Disease Research Focuses on Microglial Cells

The Human Brain

Alzheimer's Disease: “Publishing in Science Translational Medicine, the team describes
the technique as using a particular type of ultrasound called a focused therapeutic ultrasound,
which non-invasively beams sound waves into the brain tissue. By oscillating super-fast, these
sound waves are able to gently open up the blood-brain barrier, which is a layer that protects
the brain against bacteria, and stimulate the brain’s microglial cells to move in. Microglila cells
are basically waste-removal cells, so once they get past the blood-brain barrier, they’re able to
clear out the toxic beta-amyloid clumps before the blood-brain barrier is restored within a
few hours.

Photo Credit: Image: 3Dme Creative Studio /
Source: ScienceAlert

An article in ScienceAlert looks at one of the many research studies currently underway to reverse the damage caused by Alzheimer’s disease, a degenerative disease of the brain that affects 50 million individuals worldwide. In Canada, about 750,000 individuals have been diagnosed with a cognitive impairment, and 5 million in the United States.

As the population ages, the numbers are expected to rise significantly within the next two or three decades, possibly doubling or even tripling. This explains the focused scientific research to alleviate or reverse its damage to human cognition.

In the study, a team from the University of Queensland in Australia has used ultrasound waves—a non-invasive method— to help improve memory by clearing up the plaques that build up in the brain. So far, the study has been conducted on mice, where 75 percent of the mice got their memories back.

In “New Alzheimer’s treatment fully restores memory function,” (March 18, 2015), the article says:
Australian researchers have come up with a non-invasive ultrasound technology that clears the brain of neurotoxic amyloid plaques - structures that are responsible for memory loss and a decline in cognitive function in Alzheimer’s patients.

If a person has Alzheimer’s disease, it’s usually the result of a build-up of two types of lesions - amyloid plaques, and neurofibrillary tangles. Amyloid plaques sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.

Neurofibrillary tangles are found inside the neurons of the brain, and they’re caused by defective tau proteins that clump up into a thick, insoluble mass. This causes tiny filaments called microtubules to get all twisted, which disrupts the transportation of essential materials such as nutrients and organelles along them, just like when you twist up the vacuum cleaner tube.

As we don’t have any kind of vaccine or preventative measure for Alzheimer’s - a disease that affects 343,000 people in Australia, and 50 million worldwide - it’s been a race to figure out how best to treat it, starting with how to clear the build-up of defective beta-amyloid and tau proteins from a patient’s brain.
The key to solving the Alzheimer puzzle rests on allowing the brain“s waste-removal team, so to speak, do its job. These are called microglial cells, which Wikipedia says are “the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system (CNS).” 

So far this is good news for the mice; human trials are expected to begin in 2017. In another study looking at microglial cells, this one at Stanford University’s School of Medicine, in the U.S., researchers focused on blocking a receptor to improve its ability to do its job. The article, by Bruce Goldman,  is posted on Stanford Medical News.

In “Blocking receptor in brain’s immune cells counters Alzheimer’s in mice, study finds," (December 8, 2014), Goldman writes:

The researchers found that, in mice, blocking the action of a single molecule on the surface of microglia restored the cells’ ability to get the job done — and reversed memory loss and myriad other Alzheimer’s-like features in the animals.
The study, published online Dec. 8 in The Journal of Clinical Investigation, illustrates the importance of microglia and could lead to new ways of warding off the onset of Alzheimer’s disease, which is predicted to afflict 15 million people [in the U.S. ] by mid-century unless some form of cure or prevention is found. The study also may help explain an intriguing association between aspirin and reduced rates of Alzheimer’s.
Microglia, which constitute about 10-15 percent of all the cells in the brain, actually resemble immune cells considerably more than they do nerve cells.“Microglia are the brain’s beat cops,” said Katrin Andreasson, MD, professor of neurology and neurological sciences and the study’s senior author. “Our experiments show that keeping them on the right track counters memory loss and preserves healthy brain physiology.”
A microglial cell serves as a front-line sentry, monitoring its surroundings for suspicious activities and materials by probing its local environment. If it spots trouble, it releases substances that recruit other microglia to the scene, said Andreasson. Microglia are tough cops, protecting the brain against invading bacteria and viruses by gobbling them up. They are adept at calming things down, too, clamping down on inflammation if it gets out of hand. They also work as garbage collectors, chewing up dead cells and molecular debris strewn among living cells — including clusters of a protein called A-beta, notorious for aggregating into gummy deposits called Alzheimer’s plaques, the disease’s hallmark anatomical feature.
Perhaps, in the next few years, one or both methods will help reverse the terrible effects of Alzheimer’s disease. The key seems to be on the microglial cell, or at least this is the current thinking and research focus. Human cognition, our memories and our thought processes, and our abilities to make sense of our surroundings, are as much part of us and define who we are; without these, we feel lost, incomplete, angry. We wish the researchers good luck in their endeavors; this work is important, life-altering..

For more, go to [ScienceAlert] and  [Stanford]

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