What is Alzheimer’s Disease and How Are Scientists Trying to Fight it?
Cells in the Brain
Having the ability to wake up in the morning and get ready for the day is all thanks to your brain! The brain uses a variety of different cells to perform everyday functions. One of the most important types of cell in the brain are neurons. Neurons are the great communicators of the brain. They send messages from your brain to the rest of your body and receive information about what the body is doing, so that you can do things like walk and brush your teeth. A neuron is made up of three basic parts:
the cell body (soma)
branching dendrites that receive signals from other neurons, and
the axon, which sends signals out to surrounding neurons through the axon terminal.
There are other cells in your brain, called glial cells, that surround neurons. Glia comes from the Greek root for “glue”, because for a long time scientists thought that these cells were the glue that kept the brain together. Scientists now know that glial cells do way more than this! Glial cells support neurons by keeping them alive and helping them communicate with other neurons. There are several types of glial cells within the brain: ependymal cells, astrocytes, oligodendrocytes, and microglia. Microglia are thought to be the garbage collectors of the brain because they clean up the “trash” in your brain. “Trash” in your brain can be things like dead or worn-out pieces of neurons. Microglia help clean up this garbage so that the trash doesn’t build up around neurons and weaken their ability to communicate. The different cells in your brain (neurons and glial cells) need to work together to accomplish all the complicated tasks you do each day, like your math homework!
What do you think would happen if these specialized cells could no longer do their jobs?
As it turns out, it is very bad for your brain when neurons can’t communicate or if the garbage collectors (glial cells) can’t clean up the trash in your brain. When neurons and microglia can’t do their job, sometimes it can cause disease in your brain. This type of dysfunction usually causes neurodegeneration (neuro meaning brain, and degeneration meaning breaking-down). One neurodegenerative disease you might have heard of is called Alzheimer’s disease. In Alzheimer’s disease, patients develop severe memory problems because brain cells begin to die. Scientists believe that these symptoms are caused, at least partially, by a buildup of a sticky plaque called amyloid-beta.
Normally in the brain, there is a large protein called the “amyloid precursor protein” that is important for growing new neurons and fixing old neurons when they are damaged. In order for the “amyloid precursor protein” to do its job, it gets cut up into smaller pieces by other proteins. One of these smaller pieces is amyloid-beta. When a lot of amyloid-beta builds up inside of and around neurons, it creates the harmful sticky plaques. The sticky amyloid-beta plaques in the brain make it hard for neurons to send and receive information from each other, and make it hard for glial cells to clean up the brain and work with neurons. This breakdown of communication and normal cell functioning is what scientists think leads to the memory problems seen in Alzheimer’s disease. One reason that only some people have Alzheimer’s and other people don’t, is because some brains produce more “amyloid precursor protein” than needed, which is then cut and creates extra amyloid-beta proteins that eventually form the sticky plaques.
Plaque Formation and Alzheimer’s Disease
In the brain of an Alzheimer’s patient, there are two types of plaque formation. The first type are dense plaques, which is when a lot of amyloid-beta proteins clump together and form a plaque with a dense center. The second type are diffuse (loose) plaques, which is when amyloid-beta plaques build up more loosely the brain. At first, scientists tried to make drugs to get rid of all of the dense amyloid-beta plaques, but they discovered that the amyloid-beta protein by itself is important in neural repair and growth. It is just when there is an abundance of amyloid-beta protein in the brain that problems start to occur.
More recently, scientists from the Salk Institute decided to look more closely at the difference between dense and diffuse Alzheimer’s plaque formation. They discovered that microglial cells (one of the types of garbage men) break down diffuse (loose) plaques of amyloid-beta in the brain. The microglial cells will take the broken-down pieces of plaque and transport them to another compartment with the rest of the broken-down pieces of diffuse amyloid-beta plaques. Eventually, all of these pieces of plaque clump together and form the dense plaques. So, it seems that the dense plaques of amyloid-beta are actually created during the process of microglia trying to fight and destroy the buildup of diffuse plaques in the brain. This led the scientists to now believe that diffuse plaques are worse for the brain than dense plaques.
Research into Treatments for Alzheimer’s Disease
Scientists are hard at work trying to create drug therapies that prevent or destroy extra amyloid-beta from building up in the brain and forming diffuse plaques. However, drugs to treat Alzheimer’s disease are very hard to develop, and most human clinical trials have not been successful in treating or preventing the disease. Even so, the next several years will be an exciting time for Alzheimer’s researchers to take this new understanding of the disease and come up with more creative ways to hopefully cure it one day. Scientists’ goal is to find a treatment that will help prevent people from getting Alzheimer’s disease or stop it from getting worse in people that already have it. In the meantime, the best way to prevent Alzheimer’s disease is to build up as many healthy neurons as possible so that if they start to die because of this disease, there will be plenty of neurons to fill in for them and keep your memory strong.
Every year, September 21st is World Alzheimer’s Awareness Day.
Learn more at: https://www.alzheimers.org.uk/get-involved/world-alzheimers-month
References:
Costandi, M. (2018). Ways to stop the spread of Alzheimer's disease. Nature, 559(7715), S16-S16. https://www.nature.com/articles/d41586-018-05723-8
Cummings, J., Feldman, H. H., & Scheltens, P. (2019). The “rights” of precision drug development for Alzheimer’s disease. Alzheimer's Research & Therapy, 11(1), 1-14. https://alzres.biomedcentral.com/articles/10.1186/s13195-019-0529-5
Dellwo, A. (2019, Dec 01). What are glial cells and what do they do? VeryWellHealth. Retrieved September 22, 2021. https://www.verywellhealth.com/what-are-glial-cells-and-what-do-they-do-4159734
O'Brien, R. J., & Wong, P. C. (2011). Amyloid precursor protein processing and Alzheimer's disease. Annual Review of Neuroscience, 34, 185-204. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174086/
Salk Institute. (2021, April 15). In surprising twist, some Alzheimer's plaques may be protective, not destructive: Scientists find brain's immune cells form some plaques as a defense in Alzheimer's, suggesting a new therapeutic direction. ScienceDaily. Retrieved September 22, 2021. www.sciencedaily.com/releases/2021/04/210415114143.htm