Rudolph C. Hatfield, PhD., edited by Kathryn Patricelli, MA
There is no identified single cause for Alzheimer's disease. As explained in the previous section, researchers can only identify certain risk factors that can increase the chances that someone may develop Alzheimer's disease. Risk factors such as genetics, vascular conditions, a history of head injury, etc. have been explained in a previous section. The focus of this article will be on the changes that happen in the brains of Alzheimer's disease patients.
Not Normal Aging
The first thing to understand is that the normal aging process is not the same thing as the processes that interact to develop dementia. Alzheimer's disease or any form of dementia is not a result of the consequences of normal aging. However, certain processes that happen because of normal aging become amplified in people that develop Alzheimer's disease. When the brain tissue of people with the disease and those without the disease of the same age is compared it appears that people with Alzheimer's disease have a higher degree of pathology (the signs of disease) than do people without the disease. However, people without Alzheimer's disease often have some of the same changes in the brain, but to a much lesser degree. People who have more than one risk factor for Alzheimer's disease often have significantly more signs of the disease (but not always). The major signs that happen in the brains of people with Alzheimer's disease are significant shrinkage of the brain, the formation of plaques, formation of tangles, and massive cell death.
The brain shrinks to some extent because of getting older. Shrinkage with age is not unusual. Most people are aware that as people age they often get shorter because of normal shrinkage. However, in people who have Alzheimer's disease, this shrinkage is widespread. As a result, many of the neurons (the nerves in the brain) lose their connections and die. The neurons in people with Alzheimer's disease lose their ability to function, to repair themselves, and to communicate with other neurons. This process most often initially happens in an area of the brain known as the entorhinal cortex (in the temporal lobes or on the sides of the brain). This area of the brain is connected to a structure known as the hippocampus. The hippocampus is involved in many functions but one of its primary ones is to encode (create) new memories. As the neurons in this area of the brain die, the early signs of Alzheimer's disease that appear are often problems with short-term memory (the ability to remember recent information). These memory issues get worse and worse as the disease progresses.
Amyloid is a type of protein that is found throughout the body. One form of this protein called beta-amyloid 42 is believed to be toxic. In people with Alzheimer's disease high levels of this protein clump together to form plaques between the neurons in the brain. This leads to a disruption in how the cells can communicate and function. Even in elderly people without Alzheimer's disease there is often the development of amyloid plaques in the brain, but not to the same extent as happens in people with Alzheimer's disease. Researchers have not yet learned how or why this process is so exaggerated in Alzheimer's disease.
Neurons are supported by structures called microtubules. These structures help guide nutrients from the neuron cell body to the structures that receive and transmit information to other neurons (the structures known as dendrites and axons). In normal neurons a protein called tau protein attaches to the microtubules and keeps them stable. However, in Alzheimer's disease for some unknown reason, the tau protein detaches itself from the microtubules. It then sticks to other tau protein molecules that eventually tangle up and block the transport system in the neuron. This results in the neuron not being able to nourish its important structures and leads to a disruption in the communication with other neurons. Eventually large numbers of neurons die. Researchers believe that there is a connection between the formation of amyloid plaques and tangles of tau protein. As of now, they do not fully understand how this connection works or how to reverse it.
Because of the above two conditions neurons become injured and die throughout the brain. The brain begins to shrink, which is known as brain atrophy when shrinkage is significant. This leads to a progressive loss in more neurons and in a person's ability to function.
Glial cells are other cells in the brain that normally provide structure for the brain and help rid the brain of waste products. Two types of glial cells, microglia and astrocytes, absorb and destroy waste and toxins in a healthy brain. In Alzheimer's disease these cells fail to clear away waste products including amyloid plaques. Researchers are trying to find out why these cells fail to perform this vital function in Alzheimer's disease. This failure to function results in the release of chemicals that cause inflammation in the brain and results in further damage to the neurons in the brain.
As people get older the veins and arteries in their body, including those in the brain, go through age-related changes. Many people develop some level of hardening of the arteries (known as arterial sclerosis) and blockages in certain veins and arteries. In Alzheimer's disease these vascular problems may be more prevalent. This leads to reduced blood flow to the brain, which can increase the chances for inflammation and cell death.
All these processes have other consequences such as a reduction of some neurotransmitters (the chemicals in the brain that are used as messengers by neurons) like acetylcholine. Other neurotransmitters that are important for communication when released in normal amounts, but can be destructive in high amounts such as glutamate may be increased in the brain. The production of free radicals (unstable molecules that are created because of normal functioning) may also be increased. This can lead to increased tissue damage because these molecules cannot be effectively removed from the system. People who have a history of head injury are at an increased risk for development of all the above issues and this condition results in an increased risk to develop Alzheimer's disease.