“It was the summer of ’86. I was 27 years old,” recalls Tanzi. “I remember thinking that for the first time since Dr. Alois Alzheimer described amyloid in 1906, we now have a clue to its origins.”
The discoveries never stopped. Scientists around the world have continued to unravel the genetic basis of this harrowing disease that steals the mind and leaves the body empty of what it was.
Many roads lead to Alzheimer’s
With so many genes contributing to the development of Alzheimer’s disease and other types of dementia, scientists are convinced that everyone’s journey may be different.
“There’s a saying: Once you’ve seen a person with Alzheimer’s, you’ve seen a person with Alzheimer’s,” said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Schmidt College’s Center for Brain Health. of Florida Atlantic University. Medicine.
“Alzheimer’s disease is a multifactorial disease, made up of different pathologies, and each person has their own path. The disease presents differently and progresses differently in different people.”
But it is not a fact. Some people with APOE ε4 do not develop Alzheimer’s disease, while others without the gene may encounter the hallmarks of tau tangles and amyloid beta plaques.
Another pathway to Alzheimer’s is inflammation, “which is common to all chronic diseases,” Farrer said. Several new genes discovered this year appear to play a role in how the body’s immune system clears damaged brain cells.
A boost in funding
One research focus is finding therapies that target the immune system as well as inflammation in the brain, Edelmayer said, while other research is investigating cell metabolism and how cells use energy.
Scientists are also trying to understand more about how brain cells are connected and communicate through synapses, and “we’re even seeing research looking at the connection between the gut and the brain, which is another interesting focus,” he said. .
Researchers are racing to find treatment breakthroughs, aided by additional funding in recent years from the public and private sectors, Edelmayer added. The Chicago-based Alzheimer’s Association alone provides more than $300 million in funding for more than 920 projects in 45 countries.
“We want to focus on strategies that are culturally appropriate but also effective and scalable around the world,” said Edelmayer.
Search for existing drugs
Another research focus is examining existing drugs that might prevent Alzheimer’s from taking hold in the brain.
Tanzi and his team have spent seven years testing drugs that the US Food and Drug Administration has already approved on the “brain” on the plate. Since the FDA has already verified the safety of those drugs, finding a candidate from that pool would speed federal approval of the Alzheimer’s drug, getting treatments to patients faster, she said.
Tanzi also tested natural products, including herbs, spices, vitamins, minerals, and antioxidants, for their ability to affect plaques and tangles in his mini-brain creation.
“We were able to quickly screen all approved drugs and more than 1,000 natural products,” Tanzi said. “And now we have more than 150 drugs and natural products identified that could be tested in clinical trials to combat plaques, tangles or neuroinflammation.”
“It’s about giving the right person the right drug, at the right time in the course of their disease,” he told CNN.
“Many people may not know this, but after the age of 40, almost all of us start to develop the initial pathology of Alzheimer’s, which is amyloid plaque in the brain and neurofibrillary tangles,” he continued. “It’s part of life, just as most of us start to build up a little bit of plaque in our arteries from cholesterol.”
In fact, Tanzi estimates that 30 million to 40 million Americans have enough amyloid in their brains right now to benefit from a drug to reduce it, if science were able to do it safely and affordably.
“I like to say that amyloid is like phosphorous, and tangles are like wildfires that spread and spread over decades,” Tanzi said. “And along the way you’re starting big wildfires, that’s neuroinflammation.”
By the time a person shows signs of cognitive decline, he added, “the wildfire of neuroinflammation is burning,” and it’s too late to significantly rescue the brain and improve thinking and memory skills.
“The elephant in the room is that we wait until the brain deteriorates to the point of dysfunction before treating this disease,” Tanzi said. “That’s like saying wait until you lose half the beta cells in your pancreas before we diagnose diabetes.”
“Removing the amyloid at that time was not necessarily helpful,” he said. “It’s taken us some time to really understand at what point in the disease process we need to specifically target amyloid with drugs.”
lifestyle interventions
Screening tools for Alzheimer’s would speed up research and help doctors find Alzheimer’s cases at an earlier stage. However, most tests today are either invasive, like spinal taps, or hugely expensive, like positron emission tomography or PET scans, which insurance companies often refuse to cover.
“In the end, we need screening tools that are scalable, noninvasive, and certainly cost-effective for patients and their families,” Edelmayer said. “A blood test really is the holy grail if we can get there. We’re not there yet, but we’re getting close. Ask me in another two years.”
“There were actually cognitive improvements at 18 months in both women and men compared to control populations,” said Isaacson, an author of the studies. Even people who carried the APOE ε4 Alzheimer’s gene, which increases the risk of dementia in old age, saw benefits in cognition, he said.
“I’m very cautious about using words like cure,” Isaacson said. “But when we use all these various tools early, during the years leading up to dementia, I think prevention is a cure. And hopefully, risk reduction can delay the pathology long enough for the person to die of something else.” before he develops dementia.”
All of these research approaches are “bringing us to the threshold of a transformative new era in Alzheimer’s research,” Edelmayer said. “It is right now that we are facing it, especially for those currently living with the disease.”