In game-changer, Israeli researchers find Alzheimer’s markers 20 years before onset
Hebrew University-led team maps 1.65 million brain cells from 437 aging brains; innovative algorithms predict brain cells’ trajectories, bringing ‘much more hope of a cure’
Reporter at The Times of Israel
In a world first, researchers at the Hebrew University have discovered a distinct cellular pathway in the brain that indicates markers for future onset of Alzheimer’s disease, some 20 years before symptoms would be exhibited. This early detection could eventually lead to a treatment to prevent the degenerative disease.
“The study shows that Alzheimer’s disease is not just a form of accelerated aging but follows a different cellular path,” said Prof. Naomi Habib, and PhD students Anael Cain and Gilad Green of Hebrew University, who led the team of researchers at Columbia, Harvard University, and Rush Medical Center in Chicago.
Now that research has found the “molecular markers,” she said, “we can predict if an individual is on the cellular path to healthier aging, or a path to Alzheimer’s.”
This discovery will help lead toward appropriate treatments.
“We now believe we know what’s driving the disease, but we need to prove that changing the response would reverse that,” she said.
Using a data set from the prefrontal cortex of 437 aging brains, the researchers mapped 1.65 million brain cells and showed that these cellular changes — that start at least 20 years before the first signs of dementia — determine the fate of the aging brain and the progression of Alzheimer’s Disease.
The study was published last month in the peer-reviewed scientific journal Nature.
‘A huge smoothie’
Until their study, researchers only had access to post-mortem brain tissue, Habib, 45, told The Times of Israel.
This meant that scientists could only compare advanced cases of “Alzheimer’s brains with healthy brains,” she said. “We got a very biased kind of information because we had a tiny window into the late stage of the disease.”
There was also no way to isolate the different parts of the brain tissue.
“It was like we had a huge smoothie, and we had to extract all the information,” Habib said. Scientists either missed “relatively rare” molecules or “you wouldn’t know where the molecule comes from.”
But in the past few years, “with the help of an international collaboration,” she said, researchers built the data set to map 1.65 million brain cells. At the same time, Habib and the researchers developed an innovative algorithm, called BEYOND, which enabled them to examine those brain cells’ trajectories.
“We could then say, this individual is on his way to have Alzheimer’s, and that individual is actually on a different path of healthier aging,” Habib said. “We were able to untangle these two processes occurring in these aging brains and look at the entire dynamics. We can see what’s happening along the different stages.”
This was only possible with the large data set and their unique algorithmic approach, she said.
Hacking the brain
Inside the brain are supportive glial cells, called microglia and astrocytes, that Habib and her research team believe start to change at the very early stage of Alzheimer’s, responding in a way that “really shapes the outcome.”
Microglial cells monitor the brain for signs of damage or pathogens, such as bacteria and viruses, and act as the first line of defense against infections and disease.
The study uncovered a subset of these cells that drive the buildup of amyloid-β plaques, which is the initial hallmark pathology of Alzheimer’s disease.
The researchers also found changes in a group of astrocytes, which protect the brain from harmful substances in the bloodstream and directly influence cognitive decline. These changes shed more light on the complex interactions between different brain cells in the progression of the disease.
“It takes many years from the initiation event until you get the clinical prognosis of dementia,” Habib said. But by identifying the specific cells involved, “we paved the way to early identification of people at risk of Alzheimer’s disease.”
“This is exciting,” she said, “because all of this is happening before the clinical symptoms of dementia when we have much more hope of a cure.”
Devastating disease
Alzheimer’s disease affected Habib and her family personally, she said, as she watched her grandmother and other relatives suffer from memory loss and cognitive decline.
“The disease is so prevalent, and people see their loved ones suffering,” she said. “I have a lot of drive to find a cure for this devastating disease that robs people of dignity at the end of their lives.”
“People [today] live much longer and don’t necessarily have the life quality they deserve,” Habib said.
Personal awareness
Meanwhile, until a cure is found, Habib said she is “passionate” about talking to people at community centers around Israel about what they can do to prevent Alzheimer’s and age more healthily.
“I like to reach people who are not necessarily scientists and talk about healthy aging,” she said. “Of course, for most individuals, there is a genetic risk for Alzheimer’s disease, but healthy aging is also determined by your lifestyle.”
After giving a presentation about her brain research, she tries to encourage people to be aware of “the food you’re eating and the sports you’re doing and staying engaged in your community, socially and intellectually.” She stresses that they don’t have to be marathon runners but they can be a little more conscious.
“Lifestyle is not something you should start thinking about when you’re 80,” Habib said. “It’s important to lower your blood pressure and blood sugar to prevent the DNA damage and inflammation that might drive Alzheimer’s disease.”
“Even before the big discovery of the Alzheimer’s drug, which we are all working for, there are already insights that people can use in their daily life,” Habib said.
