Alzheimer’s is a mysterious disease that is often difficult to diagnose. One of the problems in identifying Alzheimer’s is that there is no one medical procedure or test that can lead to a final determination. Even the most adept neurologists are sometimes baffled. That’s because unlike a broken bone, a stomach ulcer, or diabetes, Alzheimer’s impacts the brain — the most important, yet least understood, organ in the human body. In addition, a handful of treatable conditions can mimic the debilitating effects of Alzheimer’s.
The Brain Basics
Your brain is an amazing machine. It controls every thought, every action, every touch, and every sound. Your arms and legs move because of your brain. It controls every heartbeat and breath you take. You can’t blink without your brain or move a muscle.
The brain does other extraordinary things, too. It creates and preserves memories. It is the reason we cry at weddings, laugh at a joke, or get scared watching a horror movie. Shaped like an oversized walnut that weighs about three pounds, the brain is our control center, a sophisticated communication center that makes the most powerful computer look prehistoric.
Although it is remarkable, the brain doesn’t work on its own. Blood, oxygen, and other nutrients must nourish it. The brain also needs help in sending and receiving messages. That’s the job of specialized cells called neurons. Neurons control what our body does and how it responds to our environment. The job of each neuron is to form pathways through which messages can be sent and received.
Those conduits are part of our nervous system, which, like a computer network, sends and receives messages to and from every part of our bodies. Without it, our hearts wouldn’t beat; we couldn’t think; we couldn’t laugh or smile. We wouldn’t know what day it was. Our brains are so key to who we are and how we live that when something goes haywire, when the neurons die or fail to do their jobs, our personality changes and our bodies don’t respond in the way they should.
The Onset of Alzheimer’s: Brain Attack
When Alzheimer’s attacks, it damages the brain — not all at once, but gradually, over a period
of years. The changes are subtle. Minuscule. Barely noticeable. Yet, they are real. Over time, they will become more pronounced as the brain undergoes toxic changes. The disease typically strikes first in the hippocampus, the part of the brain that allows us to process and retrieve our memories.
Think of the hippocampus as a file cabinet. When the brain makes a new, long-term memory, the hippocampus stores those memories, allowing us to retrieve them. The brain’s file cabinet is so strong that it is hard to forget the memories inside. A simple smell — a whiff of perfume, for example — or the lyric of a favorite song, can unlock the cabinet, allowing memories to escape. When we’re done with those memories, back in the file cabinet they go.
Alzheimer’s strikes when amyloid plaque, abnormal clusters of protein fragments, builds up between nerve cells in the brain. In a person with a healthy brain, these protein fragments would break down and be eliminated. As a result, the neurons continue to function as they should. Not so in an Alzheimer’s patient. Instead, the clusters bond together, disrupting the signals between the synapses, the spaces between nerve cells where information passes from one neuron to another.
The Effects of Alzheimer’s: Blocking the Brain’s Railroad
In the tissue of a normal brain, neurons receive vital nutrients along a parallel transportation system similar to railroad tracks. A protein called tau (rhymes with cow) keeps the brain’s railroad working and the transportation of nutrients on schedule. In an AD-riddled brain, however, that doesn’t happen. Strands of tau begin to break down and twist together, creating a roadblock, so-called neurofibrillary tangles, that stops nutrients from reaching the brain’s cells. Without these nutrients, the neurons die, impacting the way a person thinks and remembers. Evidence suggests abnormal tau and amyloid-beta proteins work together. As abnormal tau accumulates in specific regions of the brain, amyloid-beta clusters into plaques between neurons, disrupting the way they communicate with one another. Alzheimer’s is so tricky that scientists don’t yet know whether plaque causes AD or whether the clusters are a result of the disease.
To complicate matters, AD also attacks the cerebral cortex, the wrinkled outer layer of the brain that helps us interpret sensations from our body, such as itching or burning. It also allows us to see, hear, and smell. The cerebral cortex also plays an important role in the forming and storing of memories. It helps us formulate thoughts, solve problems, and make plans. When AD strikes, the cortex shrivels up, impacting the production of neurotransmitters, chemicals that help the brain’s neurons talk to each other. When brain cells cannot communicate, they die off. Consequently, people cannot remember things. The nerve cells affected by AD also impact the ability to speak, read, and move.
As AD progresses, brain tissue shrinks. AD’s unchecked advancement leads to the death of more cells, severely weakening the brain. To make matters worse, the body responds violently to the disease. A type of cell called microglia sets off the body’s immune response in the brain and spinal cord, inflaming the brain (even as it shrinks) and further damaging its cells. “Proteins are malforming, or changing their configuration. The brain doesn’t like that and recognizes something is wrong,” says neurologist Daniel Potts. “The immune system comes in and tries to tidy that up. It has to basically nuke some areas [of the brain] to get rid of it. You end up nuking some good tissue when you start nuking the bad tissue.”
Findings So Far
In July 2018, scientists at the University of Texas Southwestern Medical Center announced they had discovered the precise moment when healthy protein becomes toxic tau, but has not yet formed the deadly sticky tangles that choke the brain. The discovery could lead to the detection of AD before it grabs hold of the brain.
“This is perhaps the biggest finding we have made to date, though it will likely be some time before any benefits materialize in the clinic,” says Marc Diamond, M.D., director for the university’s Center for Alzheimer’s. “This changes much of how we think about the problem. We think of this as the ‘Big Bang’ of tau pathology.”
A version of this article appeared in our partner magazine Alzheimer’s: New Hope For A Cure.