The same spark that gives cancer cells their advantage may be the key to unlocking the secrets of Alzheimer’s disease for Western Biology professor Robert Cumming.
Patients diagnosed with Alzheimer’s are often found to have a buildup in the brain of amyloid beta, a protein that accumulates with age, causing plaque and impairing brain function, thus leading to memory loss. While this is the case in Alzheimer’s sufferers, there are also many adults who have this same plaque buildup but do not suffer from the disease.
“If we take some amyloid beta protein and toss it on some culture, it kills a lot of the cells, for sure, but some cells do survive,” he said. “For those surviving cells, you wonder why did that one live and that one didn’t. There are tons of elderly people wandering around, who have this plaque and no history of dementia. Why doesn’t everyone get it?”
That is the question that has haunted him since his first year at Western in 2008.
That year, Cumming taught a seminar course in cell biology where a student shared paper on the Warburg Affect, a pioneering discovery in 1920 that showed accelerated metabolism gives cancer cells a distinct advantage over normal cells. The paper was of interest because, a few years earlier, Cumming had done his postdoctoral studies at San Diego’s Salk Institute, working briefly on the idea of metabolism and its impact on Alzheimer’s.
Then and there, he started putting the two ideas together.
“I had never heard of this before. But as I read it, I thought, ‘Hey, this sounds just like what we discovered working on Alzheimer’s at the Salk institute,’” he said, describing the brain cells accelerated metabolic activity. “The surviving brain cells were ‘sugar-crazy’ and acted just like Warburg’s cancer cells.
“We looked at it from a slightly different angle, but never saw it from the perspective of cancer metabolism. Maybe this cancer metabolism we can apply to the brain since it has metabolic needs.”
The idea the Warburg Effect could apply to Alzheimer’s disease intrigued Cumming. He has since determined metabolism is a key component of the resistance mechanism. But why? Is genetic makeup acting as a protective shield? Lifestyle? Perhaps a combination?
“What is the genetic makeup of people that allows them to survive and have all this bad stuff in their brain? The biochemical processes that occur in these people and their brains; is there a drug that can activate that?” said Cumming, who is working with neuroimaging scientists at Robarts Research Institute. “Finding the mechanism by which that natural resistance occurs could give us a clue.”
While some people are able to activate this ‘cancer-like metabolism rate’ in the brain, it doesn’t mean they’re getting cancer. It simply means the cells are “sugar-loving,” taking up the body’s sugar to create lactic acid, which is then converted into energy.
“Lactic acid is produced in the brain, not at super high levels, but it has been shown, in mice, that you need to make a certain amount to enhance memory,” Cumming said. “The brain needs to break down a certain amount of sugar to generate the lactic acid.”
“In discovering this cancer metabolism, and going back to what we originally started with Alzheimer’s, we can take these cultured brain cells and specifically turn them on using genetic approaches and, low and behold, those cells are much more resistant to these toxic amyloid beta.”
Human brains are resilient and can compensate by ramping up metabolism naturally. Some people, however, may be able to ramp it up higher and maintain it for an extended period of time as they get older. Others cannot and they’re the ones getting Alzheimer’s.
“The fact people can survive with all that crap in their brain means they have a way with dealing with it,” he said. “(Researchers) became entrenched with the theory of amyloid beta causing Alzheimer’s. There’s as lot of evidence to support that. I don’t question it has a major role – but not 100 per cent. There is that 30 per cent for whom it doesn’t jive with. That’s the area we should look at. The older people who don’t get Alzheimer’s, why don’t they?
“When metabolism isn’t functioning well, it really makes Alzheimer’s take root. The ability to respond – for the brain to absorb nutrients efficiently – is definitely not right in people with Alzheimer’s. With age, this metabolism declines. So, if we can we ‘turn it on’ within the brain, and cause an increase of activation to the enzymes that promote metabolism, can we ‘turn it on’ and rescue the memory deficiency?”
Cumming said his research is “like Alice in Wonderland, going down the rabbit hole.”
“We are the first to discover this,” he said. “We are not following the beaten path. We are carving new pathways.”