Cholesterol doesn’t just clog hearts and arteries. University of Virginia researchers say it also can gum up the brain, sparking a chain of events that lead to Alzheimer’s disease.
The researchers studied cells known as astrocytes that create and distribute cholesterol to neuron cells in the brain. Normally, that’s a good thing because cholesterol helps the body produce hormones and function properly.
But too much of a good thing can be bad. When astrocytes shuttle too much cholesterol to neurons, it leads to an increase in levels of a protein called amyloid beta. That protein creates a sticky, gummy plaque that builds up on the neurons.
Plaque on brain cells, and tangles created by a protein called tau, are believed to impede the normal behavior of neurons and lead to Alzheimer’s disease and other forms of dementia. The amyloid beta that creates plaque also stimulates the creation of tau.
“This study helps us to understand why genes linked to cholesterol are so important to the development of Alzheimer’s disease,” said Dr. Heather A. Ferris, a researcher with UVa Health’s endocrinology and metabolism.
According to the study, reducing how much cholesterol is created by astrocytes results in a big reduction of amyloid beta and tau levels in the brains of mice.
Scientists have known that astrocytes change in Alzheimer’s patients but whether the changes caused Alzheimer’s or were caused by the disease was unclear. The research indicates that the astrocytes are part of the cause.
“It shows that if we can alter the production of cholesterol in astrocytes and its transport to neurons and reduce amyloid beta, we could possibly prevent plaques from ever being formed,” Ferris said.
The research also offers insights into plaque creation and could explain why genes associated with cholesterol have been linked to increased risk for Alzheimer’s. The results also give scientists important direction as they seek to prevent Alzheimer’s.
“Amyloid is sort of the trigger for Alzheimer’s disease. It triggers the formulation of tau, which makes the tangles,” Ferris said. “If we could prevent amyloid beta from being made really early in the disease, we could maybe prevent the cascade that sets off the whole string of events leading to Alzheimer’s.”
Drugs have been developed that remove amyloid from the plaque in the brains of Alzheimer’s patients, but Ferris said stopping the plaques from forming would be best.
“There’s no question that, if we could prevent them from forming rather than cleaning them up after the fact, it would be much better,” she said. “We’re using drugs in people who have symptoms now, but by the time you have symptoms, you’ve already had a lot of neuron death. We really need strategies to prevent that in the first place.”
Current medicines that limit cholesterol in the body won’t work in the brain, Ferris noted.
“It’s a little trickier than we wish it was,” she said. “The cholesterol in your blood can’t get into your brain, and the medicines we use to treat the cholesterol in your blood can’t get into your brain to treat it.”
Although different mechanisms create cholesterol in the body and in the brain, Ferris said some mechanisms that control its production are similar. For instance, insulin stimulates cholesterol production in both brain and body.
“All the good, healthy things your doctor tells you to do to limit your cholesterol, like diet and exercise, probably work for the brain, as well, but it’s really hard to measure that,” she said. “One of the strongest protective factors from developing Alzheimer’s is actually education. There are examples that show people who keep using their brain have their brains age more slowly. Exercise, both physical and mental, seems to help with the cleaning-out process.”
As for decreasing how much amyloid beta that astrocytes create, researchers say there needs to be significant research into how both the cells and the protein work inside the brain.
“If we can find strategies to prevent astrocytes from over-producing cholesterol, we might make a real impact on the development of Alzheimer’s disease,” Ferris said. “We hope that targeting cholesterol can prevent neuron death from ever occurring in the first place.”