What causes Alzheimer’s disease (AD)? You have probably seen older people with Alzheimer’s disease and know that it is a progressively crippling disease with mental deterioration, ending finally in total disability and spiraling down to debilitating frailty and death. Not a pretty site for most people. Or you may have a family member, like your mom, who may have developed this and you ask, “How did you get this, Mom?” What could you have done to prevent it?
To understand what you can do to prevent this devastating disease from happening in you, you must understand two things: 1) How the disease forms and progresses, 2) What you can do to prevent the disease. There is no treatment of the disease at present. Your best action is to do all the things needed to prevent the disease. You should start prevention early and not wait until you’re over the hill, so start now, even if you are only 30 years old.
How does Alzheimer’s disease start to happen?
If you look at a brain of a person with AD through the microscope you would see several changes to the neurons that are not supposed to be there. You would see clumps of a sticky substance called amyloid that appear to be stuck on the nerve cells in an irregular fashion. You also would see the presence of Inflammatory tangles, which kind of look like a wad of fishing line all tangled up.
At one time it was thought that the amyloid was toxic to the cells and when accumulated on the neurons it resulted in the damage that results in AD. This may be the case in the inherited form of AD (i.e. young onset; around age 50) but may not be the case in the most common form of AD that forms as you get older. It may actually be an attempt to repair the cells, but too much damage occurs so you get too much sticky gum on the neurons possibly slowing their conduction.
The incidence of AD is around 10% of the general population, most of which is the common type. It is the one that you see in older people, generally at least over the age of 55. The hereditary form comprises only about 1% of the cases of AD, and generally occurs when the person is younger, i.e. under the age of 55. Both end up with the same devastating debilitation that you see with AD. Since we can do something about the most common form, we’ll discuss that one.
It is now thought that AD starts with metabolic stress in the brain. This is essentially the formation of excess free radicals within the cells and, specifically, the mitochondria within the cells. The mitochondria are the powerhouses of the cells. They are continually exposed to constant electrical activity to make our power molecules (ATP), which is their main function
Think of mitochondria like a power plant that’s producing electricity. The electricity powers mechanical stuff that we use by the flow of electrons through the wires. However, occasionally “shorts” happen, which can damage the wires and anything that’s near it. Have you ever shorted out something and saw the damage? That’s what we’re talking about.
The mitochondria produce energy in the form of ATP. This is a highly energized molecule that fuels every function of your body, from moving your arms to thinking about your next conquest. ATP is like the electricity of your cells. During its formation, free electrons may form called reactive oxygen species (ROS), which can damage structures, like the short at the electrical plug.
It is now thought that AD starts by the excess formation of these ROS, which then damage the cellular structures near it, which may be the membranes, DNA, mitochondria per se, or other tiny structures within the cells. Microscopically, this damage then sets up a cascade of events which, if not corrected properly, may result in AD within the brain.
ROS Triggers Amyloid Production and Inflammation
Your body was built to repair itself down to the micro level. If you cut yourself, your body repairs the cut. If you bruise yourself, your body dissolves the bruise. What’s not right your body has systems that repair it and correct the problem. This is you immune system at work. At the cellular level, if ROS damages your mitochondria and the surrounding parts of the cell, your body’s reparative actions are triggered to repair the damage and make it better.
This reparative process includes two actions within the brain. The ROS damage triggers the cells to produce amyloid, sort of like a sticky band aid on the damaged neuron, and it triggers cells within the brain called microglia to fix the damage. These microglia are part of your immune system, which does a plethora of actions from identifying a problem, sending cells to fix the problem, and cleaning up the mess from the problem.
Part of the mess is the amyloid. The microglial cells are the brain’s macrophages: they literally eat up the mess. They are like an army of cells that swarm around the amyloid accumulations, called plaques. Essentially, they invade the plaque and try to repair the damage while cleaning up the damage, which results in a lot of collateral damage and accumulation of inflammatory cells, otherwise called inflammation.
You have probably seen people who have inflammation of their hands due to arthritis. Their fingers become inflamed with pain. The result is destruction of the joints, which then causes deformities of the joints, debilitation, and even more pain. Pain can be a sign of destruction of the tissue. However, in the microscopic environment of the brain, you don’t feel the pain. Thus, you don’t feel the destruction that may be happening there. And the destruction that leads to AD can begin 20 years or more before you actually see symptoms of AD.
The inflammatory damage causes further destruction to the nerve cell walls, called the cytoskeleton of the cells, and ultimately these walls collapse. Nerve cells are long, like microscopic fishing line, with a tiny body sending out the signals. When the damage to the exoskeleton is severe, the cell collapses and forms into a tangle of fibers called neurofibrillary tangles. These look like small tangled clumps of fishing line. Of course, when they happen, the neuron is dead and functions no more.
After a lot of these neurofibrillary tangles form from the excess ROS damage, you start to see a significant amount of brain dysfunction. Your memory becomes bad and you just are not able to function adequately in this world. As this process continues, your mind goes. You don’t think well, you don’t remember things and people, and ultimately the destruction of the brain cell results in the frail AD patients that you may have seen who die through a slow sad death spiral.
Since none of us wants to suffer from this, there are things that you can do to prevent this destruction from happening, which we’ll discuss in Part 2 of this series. (TO BE Continued)
 Geldmacher DS. Alzheimer disease prevention: Focus on cardiovascular risk, not amyloid?. Cleveland Clinic Journal of Medicine. 77(10). Oct 2010:689-704. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/issues/articles/media_e3acdb4_689.pdf