ST. LOUIS — Alzheimer’s disease affects an estimated 6.9 million Americans, but there’s no way to study the disease in the lab, making finding a cure nearly impossible.
University of Washington researchers have found a way to simulate the progression of Alzheimer’s disease outside of living patients, allowing it to be studied accurately in the lab — an advance that could simplify and accelerate the development of treatments and preventions for the disease.
The findings were published Thursday in the journal Science.
“Millions of people have Alzheimer’s disease, but for the later-onset form that 95 percent of patients experience, there has been no validated human model,” said Chao Sun, a research scientist at the University of Washington and first author of the study. “Now we can devise patient-specific models in a culture dish.”
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Alzheimer’s affects neurons, the brain’s communication cells, and the neurons grown in the lab are all young, which isn’t exactly ideal for studying age-dependent diseases, unless you can wait 60 years until you’re old enough to get the disease.
Scientists at the University of Washington are essentially asking: Can we mimic the progression of Alzheimer’s disease outside a patient’s body — in a petri dish or a beaker — and poke and prod until we find a way to stop it?
This mindset would be especially useful for Alzheimer’s, which affects 95 percent of patients – age-related or sporadic.
As both names suggest, the disease worsens as patients age, and its causes are complex and poorly understood.
Scientists believe that age-related Alzheimer’s disease is caused by an intersection of a patient’s genes, lifestyle and environment, making it difficult to replicate studies in highly controlled laboratory settings.
But it’s been more difficult for scientists to address the age component of the disease in their studies.
While there are ways to grow Alzheimer’s-like neurons in the lab, accurately replicating how the disease progresses over time and over age in humans is crucial to developing drugs that are more likely to succeed in clinical trials in mice and then in humans.
This is where the University of Washington study comes in: The aim of the study was to generate neurons in the lab that were the same age as patients suffering from the disease, the authors said.
They have discovered a way to create neurons in the lab that “behave in an age-appropriate manner.”
Because it is not possible to safely extract neurons from Alzheimer’s patients, or any other patients, most researchers take cells that are easier to access, such as skin cells, and convert them into neurons.
The University of Washington researchers are using a unique combination of cellular machinery to make this switch without erasing the age of the cells taken from a patient.
“We’re thinking about cell fate in a slightly different way,” said Andrew Yu, a professor of developmental biology at the University of Washington and lead author of the paper.
The researchers performed a series of tests to determine how similarly the lab-grown neurons behaved to neurons from people with age-related Alzheimer’s disease.
The lab neurons passed all the tests: They formed troublesome protein complexes that normally interfere with brain function in Alzheimer’s patients and deteriorated rapidly over time.
This system is the first of its kind to allow scientists to precisely study the aging brain, without waiting until it’s too late.
“If a patient dies, their family can donate the brain for scientific research and it can be studied that way, but other than that, we don’t currently have the technology to study the function of a living brain in 3D,” said Dr. William Maurice Redden, a geriatric psychiatrist at Saint Louis University.
This new study could change that by providing a human cell system to understand disease progression and test potential treatments.
Redden said there are very limited treatments for Alzheimer’s disease, and no treatments can restore cognitive function lost due to the deterioration of patients’ neurons.
Yu said the new model of Alzheimer’s has already proven useful in identifying the genetic causes of age-related Alzheimer’s.
“We were trying to figure out what makes neurons angry as we age,” Sun said. Neurons in the study showed signs of inflammation, which is common in the brains of people with Alzheimer’s, but scientists didn’t think the neurons would cause it themselves.
Sun said it had always been thought that inflammation in patients was caused by neurons interacting with the immune system, but it turns out neurons can initiate the inflammatory process themselves.
The researchers wanted to know how these neurons were causing inflammation, and because “transposable elements” — small segments of DNA that can essentially be copied and pasted anywhere and at any time on the genome (including into the way of important genes) — have been shown to play a role in inflammation in the past, the authors decided to investigate this pathway further.
“As we age, everyone experiences changes in translocation elements, but the key here is that healthy neurons are able to cope with these changes,” Yu says. “Alzheimer’s neurons have a harder time dealing with these changes.”
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