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The Alzheimer’s Breakthrough That’s Been Missing Until Now—The Third Dimension

Neuroscientists at Massachusetts General Hospital announced that they successfully grew human neurons in 3D in tiny petri dishes and, in the process, said they have solved one of the key mysteries of Alzheimer’s.

ByTim De ChantNOVA NextNOVA Next
Tangles that form between the 3D web of neurons in our brains are a key trait of Alzheimer's.

Scientists think they have uncovered a key characteristic that’s been missing from Alzheimer’s research—the third dimension.

Rudolph Tanzi and Doo Yeon Kim, neuroscientists at Massachusetts General Hospital, announced yesterday that they had successfully grown human neurons in 3D in tiny petri dishes and, in the process, said they have solved one of the key mysteries of Alzheimer’s. Their finding could pave the way for rapid testing of drugs to treat the disease, reducing the time needed to receive preliminary results from many years to mere months.

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For decades, researchers have been studying the disease using mice modified with a gene that’s known to cause Alzheimer’s in humans. But the findings of those studies haven’t translated well to humans, in part because while the mice developed amyloid beta plaques in their brains—one trait of Alzheimer’s—they never seemed to develop tangles of Tau proteins—another hallmark of the disease. In humans, the brains of full-blown Alzheimer’s patients have both.

Kim suggested to Tanzi that they grow human neurons with an Alzheimer’s mutation in a gel, which would allow the cells to form a three-dimensional web that more closely mimics the structure of the human brain. Almost immediately after starting the experiment, they noticed the dishes contained plaques. A bit later, they spotted tangles. That the tangles appeared after the plaques seemed to confirm a longstanding hypotheses about the disease—that tangles form in response to plaques. That insight could lead researchers to develop new treatments to slow the progression of Alzheimer’s or ward it off entirely.

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The new “Alzheimer’s in a dish” approach, as Tanzi, Kim, and their colleagues call it, could hasten the testing of drugs targeting the disease. Here’s Gina Kolata, reporting for the New York Times:

Dr. Tanzi is now starting an ambitious project to test 1,200 drugs on the market and 5,000 experimental ones that have finished the first phase of clinical testing — a project that is impossible with mice, for which each drug test takes a year. With their petri dish system, Dr. Tanzi said, “we can test hundreds of thousands of drugs in a matter of months.”

The study also suggests that early intervention could be key in halting Alzheimer’s. If tangles do form in reaction to plaques, then stopping the formation of plaques could be key. Results from a recent clinical trial performed by Genentech appear to support that hypothesis. When patients with mild to moderate Alzheimer’s were given crenezumab, an engineered antibody that binds to amyloid beta proteins, those with mild symptoms didn’t decline as quickly .

While the new study is a breakthrough for Alzheimer’s research, the idea of simulating diseases by developing 3D in vitro models isn’t new. Devices called organs-on-a-chip use the third dimension to mimic human structures like alveoli in the lungs. While not every part of the human body has been recreated in a dish just yet, researchers have been making consistent progress, meaning that one day, animal models may no longer be needed to study human diseases.

Rudy Tanzi explains the goals of his lab in 30 seconds. For more on Tanzi, visit his profile at NOVA’s The Secret Life of Scientists and Engineers .

Image credit: Stacy Jannis, William Dempsey and Rebekah Fredenburg; Jannis Productions/NSF