Alzheimer's and the Brain
Hey, Vsauce. Michael here.
If you have a watch or a clock nearby, take a look at its hour hand. It moves, completing a trip all the way around twice a day. Its motion is too slow to see, but try really look at it right now. Watch how far it travels in one second. Okay, one Mississippi, done. That's it; see how far it moved? Well, if this watch was the Milky Way, that would be about how far we have traveled in our solar system around our galaxy since the invention of writing, since the beginning not of time but of our history. It's a very small distance, unnoticeable for most of humanity's existence. There haven't been writing, physical recordings of events or ideas.
Today, of course, we have writing, and we have many different ways to physically store data. We even now have digital ones. But before writing was invented, all humans had was biological storage: memories. There was no encyclopedia, no phone book, no library. But what there was, was old people. Everyone around, they've experienced the most, heard the most things, had the most thoughts. Even today, with all this stuff around, the oldest among us remain the libraries of things that physical and digital libraries either don't, haven't been, or can't yet chronicle. Aeschylus famously said that memory is the mother of wisdom, but like all storage formats, individuals don't last forever. These can be lost, we can die, these can obsolesce. They can still be around but have no way to be played back or read; they can be abandoned, ignored. These can also just wear out, just as we can forget or develop dementia.
Dementia involves a decline in cognitive skills used to perform everyday activities. Sixty to eighty percent of dementia cases are Alzheimer's. The disease is associated with the accumulation of plaques and tangles in the brain, changes accompanied by damage to brain cells and their death. The older a person is, the more likely they are to have developed Alzheimer's, but Alzheimer's is not a part of normal aging. Symptoms of Alzheimer's disease include a decrease in the ability to think and remember, confusion about time and place, new difficulties speaking and writing, changes in mood and personality.
As we fight against other diseases and live longer lives, Alzheimer's looms on the horizon as if waiting for us to pass the test of other challenges as a cause of death. From 2000 to 2013, many things decreased, but Alzheimer's has grown. Stopping it, preventing it, postponing its development in our brains long enough that we at least die of something else with our memories is a real goal we can achieve.
Your brain fits inside this thing: your skull, specifically this part back here called the brain case, or the cranium. It's a bone fortress protecting an inner sanctuary called the cranial cavity. Your brain sits right here—except it doesn't really sit so much as it swims. You see, the brain is incredibly fragile, soft, and gooey. Model or toy brains tend to be made out of rigid plastic, and actual specimens used in dissection tend to be rubbery because they've been affected by chemicals like formaldehyde. But real raw fresh brains, right out of someone's brain case, are soft, like soft tofu. Holding one like this for too long will leave a lasting and shaped depression.
For that reason, the brain has to float, so it doesn't crush itself under its own weight. But it doesn't float in water; instead, it floats in a special liquid your body makes called cerebrospinal fluid.
Now, this isn't a whole brain; this is just the cerebrum, the largest part of the brain. It plays a key role in language, thought, abstract thinking, awareness, consciousness. It thinks it's a pretty big deal—literally. It's the part of you that does speaking. Anyway, the outside of the cerebrum is called the cortex. Cortex means bark, like tree bark or a ride or a husk. If I tear off one of the temporal lobes, we can take a closer look at this rind. It's painted in maroon; here you can see its extent. It's only about two to four millimeters thick. It's often called gray matter because it appears pinkish, yellowish, gray in a real brain. Beneath it is the white matter, white because although gray matter contains a lot of cell bodies, the white matter contains mainly axons that are myelinated—that send messages from gray matter to gray matter locations.
Myelin is a whitish material that insulates electric messages, allowing them to move faster. And fast they do move; signals travel through axons at up to 432 kilometers per hour—that's 275 miles per hour, about the top speed of the fastest production car in the world. You can say this car literally travels at the speed of thought, but that's slow compared to the speed of electricity through a conductor, which is closer to 50 to 99% the speed of light.
Anyway, the brain is very wrinkly, and that's because a wrinkled shape allows more cerebral cortex to fit into a smaller container. If we could take this entire line, all of your cerebral cortex, flatten it out, it would be well, about like this. It would be about 2 to 4 millimeters thick and have an area equivalent to a square 50 centimeters by 50 centimeters, about 20 by 20 inches. Obviously, you can't fit this shape into this shape unless you crumple it up. And now we're getting somewhere.
When we crumple the brain up, we get folds. The folds are called gyri; cingular gyrus, and the crevices are called sulci; singular sulcus. About two-thirds of your cerebral cortex is buried deep within sulci, out of view.
As for memories, well every time you learn something new or memorize something new, your brain doesn't gain another wrinkle or anything like that. Instead, memories appear to be more about connections, relationships, and patterns formed by connected neurons. When neurons fire together again and again, rehearse their connections, and bonds become stronger, they become more likely to fire together again to be recalled. Roughly, that might be how memory works, and it's a helpful way to think about some interesting phenomena, like the fact that it's quite difficult to list off the name of every book you've ever read.
That's like really difficult! But if someone were to just name book titles, you could effortlessly tell them whether or not you read the book. Hearing the title likely excites neuron connections more directly involved with the connections associated with your memory of having read that title than a mere prompt to name some books you've read.
When brain cells and their connections are damaged, blocked, compromised, or killed, memories conveyed and the formation of new memories can be hampered. Learning how this happens in Alzheimer's isn't just important for those diagnosed but also for all of us interested in memory.
In one to five percent of Alzheimer's cases, genetic differences can be identified, but the cause of most cases is still mostly unknown. A number of hypotheses and observations exist. For example, we know that 15% of individuals with Down syndrome who live 40 years or longer develop Alzheimer's disease, and 50 to 70 percent of those who live to 60 do. Down syndrome is caused by the presence of all or part of a third copy of chromosome 21.
We still have a lot to learn, but chromosome 21 is also involved in the plaques found in the brains of people with Alzheimer's. Within this chromosome are the genetic instructions for the production of a protein called amyloid precursor protein, or APP. APP seems to play a role in neural growth and repair; it's found on cells throughout the entire body.
It's processed by the body in different ways, most often an enzyme called alpha secretase cleaves it into sAPPα and C83. Less often, an enzyme called beta secretase snips APP a bit higher up, releasing a smaller fragment called sAPPβ. A third enzyme can gamma-secretase and cleave AICD away, leaving p3. If alpha secretase acted first, then beta-amyloid if beta secretase acted first.
The normal function of beta amyloid isn't exactly known yet; it may play an important role in healthy brain function, but if too much is made—or maybe if too little is cleared away too slowly—or if the protein folds in the wrong ways, fragments can stick together, creating oligomers, groups of a few pieces, say four or five.
These oligomers can then stick to other oligomers and become larger structures called plaques. The effect oligomers and plaques have on brain cells and brain health is being studied. Oligomers may be more toxic; they may allow unregulated ion flow into neurons, causing their deaths. What we do know is that Alzheimer's disease is associated with these plaques in the brain, as well as another protein-related anomaly: tangles.
A protein called tau stabilizes microtubules in brain cells, like railroad ties holding tracks together—the tracks that guide nutrients and other molecules throughout the cell. In many neurodegenerative diseases, tau proteins become abnormally sticky and tangled with other tau proteins, compromising the delivery network.
We do know some factors associated with increased or decreased risk, but their exact relationships with cognitive decline aren't all certain. Things associated with a reduced risk for Alzheimer's disease include physical activity, a heart-healthy diet, learning a second language later in life, being social, frequently interacting with people, protecting your head, and intellectual activities like crossword puzzles, playing instruments, reading, board games, education.
Such activities may improve overall brain health and cognitive skills, with a brain more resilient to damage should it come. Whatever the case, there's a lot more we can learn. It is incredible and exciting and a little scary to realize how much more we have to learn about the brain.
We know more about the orbital mechanics of distant binary stars than we do about the very mechanisms we use to know about them in the first place. Inner space is as mysterious and deep as outer space, and of course, between the two, one doesn't even care if we exist while the other—well, the other is us, the wobbly gel in our heads.
No stiffer than a good booger, it is fragile and still very much of a scientific frontier. It looks like soft meat but it can not only think, reason, feel, remember, and lie, it can also care for other people and the goopy wrinkled things inside their skulls. It can be patient with them, see them as people no matter how they change—whether by growing up or growing way up. Supporting research, caregivers, and those diagnosed is something we can all do.
So thank you, and as always, thanks for watching.
Terry Pratchett famously said that right now, the sword that will defeat Alzheimer's is probably made of gold. Donations and resources for the last few years, Vsauce has donated to and supported the Alzheimer's Association. They are great people, and they helped me a lot with this video. I've included links to them in the video's description.