Understanding Alzheimer’s Disease: A Neurodegenerative Mystery
Imagine your life being taken from you, in front of your own eyes.
One day, everything feels normal. But soon, something is off. The world begins to blur from your memory and slowly but surely, you struggle to remember how to do simple things.
All of a sudden, you can’t walk down the stairs or tie your own shoelaces. You feel helpless, embarrassed, weak, and as if you are physically and mentally falling apart.
Before long, you can’t comprehend the world around you. Unable to recognize your surroundings. You struggle to recognize and name your friends, children, grandchildren, and neighbors even though you’ve known them for decades.
Soon, you aren’t even sure of your own identity.
This is what life is like for 50 million people around the world.
Alzheimer’s is the sixth-leading cause of death in the United States. If scientists are unable to find any sort of cure, global rates of dementia could exceed 152 million people.
However, there is a problem.
It is impossible to find a cure before we even know the cause.
Unraveling the Mystery
Alzheimer’s Disease is a form of dementia, an umbrella term for memory loss and developed cognitive impairments that are severe enough to interfere with daily life. It is by far the most common form of dementia, accounting for 60 to 80 percent of all types.
Since Alzheimer’s worsens over time, it is considered a progressive neurodegenerative disease. Early stages are mostly limited to difficulty retaining new information. After several years, symptoms worsen dramatically. Most often, the symptoms of late-stage Alzheimer’s include:
- disorientation
- severe mood and behavioral changes
- constant confusion regarding surroundings and events
- unawareness of time and place
- irrational thoughts and suspicions
- more serious memory loss
- difficulty swallowing, speaking, and walking
Although Alzheimer’s disease is frequently excused as old age or weakened memory, it is not a normal part of aging. While increased age is the most well-known factor, approximately 200,000 Americans under the age of 65 have Alzheimer’s as well, a form known as early-onset Alzheimer’s disease.
Neurons: The Real Nemesis
Our brain contains 100 billion nerve cells, known as neurons. These specialized cells process and transmit information throughout the nervous system through electrical and chemical signals.
The neuron has three main parts: the cell body, dendrites, and the axon.
The cell body of the neuron contains the nucleus. If you recall ninth-grade biology, the nucleus houses the neuron’s genetic blueprint that directs and regulates the cell’s activities.
The dendrites are branch-like structures that extend away from the cell body. They collect signals from other neurons and transmit those messages to the cell body.
The axon is essentially a tube-like structure carrying an electrical impulse from the cell body or another cell’s dendrites to axon terminals; structures at the opposite end of the neuron. From there, the signals can transmit to other neurons.
The function and survival of neurons are based on a few key biological processes:
Communication
Because of their structure, neurons are constantly in contact with their neighboring brain cells. When a neuron receives signals from other neurons, it generates an electrical charge that travels down the length of its axon and releases neurotransmitter chemicals across a tiny gap, which is called a synapse.
Like a key fitting into a lock, the neurotransmitter molecules bind to specific sites, called receptor sites, on a dendrite of a nearby neuron. The activity of the neuron receiving the signal is now either stimulated or inhibited depending on the neurotransmitter and binding site. A single neuron might have as many as 7,000 of these connections.
Metabolism
Metabolism is the breakdown of chemicals and nutrients with a cell. Neurons require energy, in the form of oxygen and glucose, which is found in the blood circulating through the brain. Once the neurons collect glucose, it is metabolized by the mitochondria into cellular energy. Most of the glucose consumed by the brain is used to maintain synaptic function and meet the energy demands from the high volume and vast surface area of dendrites.
Repair, Remodeling, and Regeneration
Unlike somatic cells, which survive for no more than about 4 months, neurons have evolved to live in humans for over 100 years. Therefore, it is critical that they are constantly repairing themselves to preserve their function.
In addition, neurons constantly adjust or “rewire” their connections based on their surroundings. They have the ability to strengthen, weaken, or even break down connections with one group of neurons and build them with another group. Adult brains can even conduct a process called neurogenesis; the generation of new neurons.
Wait, are neurons the only cells in the brain?
While neurons are the major contenders of the Central Nervous System, they aren’t the only ones.
In reality, glial cells are the most numerous in the brain and outnumber neurons by around 10 to 1. Glial cells are non-neuronal cells in the brain and spinal cord. They surround and support the function and health of neurons. Although they come in many forms, they work with various other cells, such as the blood vessel cells in the brain, to maintain balance and optimal function.
The Manifestation of Disease
It is typical for the brain to shrink during healthy aging, but in Alzheimer’s disease, the damage is widespread. Large numbers of neurons stop functioning, lose connections with other neurons, and die. The disease disrupts the vital processes described above; communication, metabolism, and repair.
Alzheimer’s disease manifests long before it can be externally detected. The stages when Alzheimer’s manifests are called the preclinical stages and are rarely identifiable. Neither the patient nor their friends, family, and doctors are able to detect any symptoms. This stage can last for years if not decades.
The disease initially begins to destroy neurons in parts of the brain that are correlated with memory. These include the entorhinal cortex and hippocampus regions. From there, the disease spreads to the cerebral cortex, which is responsible for reasoning, language, and social behavior. As the disease progresses and spreads throughout the brain, the patient loses his or her ability to function independently. Eventually, the disease becomes fatal.
After decades of research, scientists are still unable to find the root cause of Alzheimer’s. However, there are two main hypotheses that are widely accepted by the scientific community.
Amyloid Plaques
The first hypothesis is known as the amyloid hypothesis. This hypothesis is based on scientists’ observations of a protein in the brain that is known as amyloid precursor protein, or APP. Although scientists have not yet found APP’s normal function, they have found that it cuts into smaller sections when activated to do its job.
One of the fragments that are formed is the protein beta-amyloid. Beta-amyloid is a prime suspect in Alzheimer’s disease because it is chemically “stickier” than the other fragments APP produces. Beta-amyloid aggregates in microscopic plaques, which are almost always found in an Alzheimer’s patient.
Initially, the protein aggregates in smaller clusters called oligomers, then into chains of clusters called fibrils, mats of fibrils called beta-sheets, and eventually into plaques, containing clumps of beta-sheets and other substances.
Specifically, the amyloid hypothesis suggests that the different stages of beta-amyloid aggregation disrupt neuron communication and activate immune cells, which in turn trigger inflammation. Eventually, this leads to the destruction of brain cells.
Neurofibrillary Tangles
The second hypothesis for Alzheimer’s disease is known as the tau hypothesis. This hypothesis looks at neurofibrillary tangles, which are abnormal accumulations of a protein called tau that is collected inside neurons.
Healthy neurons are supported internally by structures called microtubules. Microtubules help guide nutrients and molecules from the cell body to the axon and dendrites. Within the neuron, tau binds to the microtubules and helps to stabilize them.
In Alzheimer’s patients, abnormal chemical changes cause tau to detach from the microtubules and stick to other tau molecules. This forms threads of tau, that eventually become tangled inside neurons. The tangles are harmful as they block the neuron’s transport system, blocking the synaptic communication between neurons.
Despite these two separate hypotheses, recent evidence shows that Alzheimer’s disease is most probably caused by complex chemical interactions between both abnormal tau and beta-amyloid proteins among several other factors. Specifically, scientists have found that as the beta-amyloid aggregation nears the “tipping point,” there is a rapid spread of tau throughout the brain.
What Can We Do?
Right now, there is no cure for Alzheimer’s. Due to the complexity of the disease, it is improbable that one single drug or treatment will be the solution. For the most part, doctors and caretakers focus on helping patients maintain mental function through cognitive exercise, managing behavioral symptoms, and reducing emotional and physical pain.
Along with drugs to aid with sleep, anti-anxiety drugs, anticonvulsants, and antipsychotics, several prescription drugs are approved by the FDA to hinder the growth of the disease. However, most of the drugs work best for early and middle-staged patients. While these drugs can subside the pain and slow down some symptoms such as memory loss, none of the medications can stop the growth of the disease itself.
Medications such as cholinesterase inhibitors and memantine will only prove to be effective for so long.
Research on Alzheimer’s Disease has developed to a point where scientists can focus on finding the underlying causes for sicknesses instead of focusing on treating symptoms themselves.
Researchers are continuing to conduct clinical trials to explore possible treatment options. A possible solution is the removal of beta-amyloid plaques through activation of the immune system. Other research looks at the inhibition of the Fyn protein, which interacts with beta-amyloid, gene editing to block the enzymes involved with the production of beta-amyloid, researching ties with insulin resistance, hormone therapy, and other potential treatments.
But what can we do?
Informing others is the first step to eradicating Alzheimer’s. It is impossible to address the issue if society is unaware of it in the first place. By visiting patients, understanding the science, and even reading articles like this one, we can increase funding and attention towards the disease.
In addition, we must continue to support organizations such as The Alzheimer’s Association, a non-profit organization leading the way in accelerating global research, driving risk reduction and early detection, and maximizing quality care and support.
Meanwhile, it is important for us to cherish our relationships with those around us, especially our elders. Showing our appreciation and spending time with our parents, grandparents, and family is a gift that many of us so easily undermine. After all, it is not what we have in our lives, but who we have that counts.
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