Read here the full transcript of neuroscientist Courtney Glavis-Bloom’s talk titled “Rethinking The Link Between Alzheimer’s And Aging” at TEDxSanDiego 2024 conference.
Listen to the audio version here:
TRANSCRIPT:
A Personal Experience with Alzheimer’s
Late one night, when I was in high school here in San Diego, on the other end of the line was the Houston Police Department. They were calling to let us know that my grandfather had dropped my grandmother off at a pizza restaurant at three o’clock in the morning. He did this because he didn’t recognize her, and it was his method of removing a stranger from his house. But the real underlying reason is because he had Alzheimer’s disease.
Alzheimer’s is so prevalent that it’s likely everyone has been impacted in one way or another: as a friend, a caregiver, a family member. Scientists have spent decades studying Alzheimer’s disease, but there still isn’t a cure. The limited options that exist for treatment help some symptoms, just a small bit, and only temporarily.
This is disappointing for sure. But it’s not all that surprising, given that we still do not understand the biggest risk factor for getting Alzheimer’s disease in the first place: aging. It’s time for a new approach.
A New Approach to Alzheimer’s Research
One that prioritizes an understanding of why aging is the single most significant risk factor for getting Alzheimer’s disease. An approach that recognizes that without a comprehensive understanding of normal, healthy aging, curing the diseases that arise because of it will remain elusive. As a neuroscientist at the Salk Institute, my colleagues and I have adopted this approach. Critical to our work is the fact that aging is inevitable.
It happens to everyone. But thankfully, cognitive decline doesn’t. And so before we can solve Alzheimer’s disease, we must first ask what biological differences determine whether someone ages with or without cognitive decline.
Identifying the biological changes that occur with aging
Understanding how these changes are interconnected
Knowing the sequence in which these changes occur
Meeting these objectives requires a strategy that explores aging not as a single event, but as the dynamic process that it is. A process that unfolds over a lifetime. But humans live for a long time.
The Marmoset Model
And the immediate and growing concern of Alzheimer’s disease means there’s an urgent need for answers. We can’t afford to wait decades for these answers. And so we’re not waiting. We are studying aging in marmoset monkeys.
Marmosets live just 10 to 12 years, which means that we can study their entire lifespan in a fraction of the time it would take to do the same work in humans. And what we discover about marmoset aging is directly applicable to humans, because marmosets and humans are both primates, and so they have brains that are remarkably similar. Also, marmosets are smart.
But we can’t ask them questions because they can’t talk. So how do we know if they’re experiencing cognitive decline? We taught our monkeys to use touchscreen computers. And then we let them play video games.
But we’re not talking about Super Mario Brothers. The video games that we designed for the marmosets are similar to the tests used to diagnose memory problems in people. And so by tracking how well the marmosets perform on their video games, we can measure how well their brains are functioning as they get older. On the screen, you can see Triscuit getting ready to play a video game that measures his memory.
You can play along with him. After he starts the game by touching the blue square, the goal is to identify each new object as it’s added to the screen. Now, similar to what’s found in people, some of our marmosets are continuing to perform really well on their video games as they get older.
And they demonstrate cognitive resilience. But other marmosets are starting to struggle on their video games. And they’re starting to show some cognitive decline. This has let us start to explore what biological differences explain cognitive resilience versus cognitive decline.
The Brain’s Energy Demands
One of the biggest clues we have is the fact that the brain uses a whopping 20% of the energy the entire body requires, even though it makes up just 2% of the body’s weight. What does the brain need all of that energy for? Well, most of it goes into helping brain cells, called neurons, talk to each other. This communication between neurons is a critical part of the way our brains work to help us think.
And reason and solve problems. When neurons communicate, they send information across tiny gaps between them called synapses. The larger the synapse, the more information can be sent. But the more energy it takes to do so.
Energy for communication between neurons is made by parts of cells called mitochondria that act as tiny power plants. And they come in different sizes, with larger ones producing more energy than smaller. For seamless communication between neurons, the size of mitochondria must match what the synapse needs. In other words, energy supply must equal demand.
The Key to Cognitive Resilience
This means that mitochondria need to be the right size for the synapse they’re working with. And this is exactly what we see in the brain of an aged marmoset with cognitive resilience. The matched sizes of mitochondria and synapses mean there’s a match between energy supply and demand. This leads to seamless communication between neurons, which is critical for good cognitive functioning.
In contrast, in the brain of an aged marmoset with cognitive decline, the sizes of mitochondria and synapses do not align. This means there’s a mismatch between energy supply and demand, which disrupts communication between neurons. And when neurons can’t communicate, cognitive decline sets in. This discovery has opened an entirely new way of thinking about cognitive decline with age.
It didn’t come from studying Alzheimer’s disease directly, but by seeking to understand its biggest risk factor, aging. And as is the way in science, answering one question begs several more that have shaped our ongoing research directions. We recognize that the brain is not operating in isolation. It is part of an entire body undergoing the process of aging.
And so we’re exploring what else we can learn about aging by studying things like blood and fecal samples from the very same marmosets whose video game performance we’re tracking. We are confident that our approach will lead to novel insight into why some people age with cognitive resilience and others age with cognitive decline. And with new understanding about aging, doors will be opened for groundbreaking treatments for diseases that arise because of it, like Alzheimer’s. I envision a future where cognitive resilience is just as inevitable as aging.
