Fighting Alzheimer’s Disease: Where Are We Now?

“It was the summer of ’86,” Tanzi recalls. “I was 27 years old.” “I remember thinking that for the first time since Dr. Alois described amyloid in 1906, we now have evidence of its origins.”

The discoveries did not stop. Scientists around the world have continued to shed the genetic basis of this heartbreaking, mind-robbing disease, leaving the body empty of its former selves.

There are many ways that lead to Alzheimer’s disease

With so many genes contributing to the development of Alzheimer’s disease and other types of dementia, scientists are convinced that each person’s journey may be different.

“There’s a saying: As soon as you see someone with Alzheimer’s, you see someone with Alzheimer’s,” said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic in the Center for Brain Health at Florida Atlantic University Schmidt College. medicine.

“Alzheimer’s disease is a multifactorial disease, made up of different diseases, and everyone has their own path. The disease manifests itself differently and develops differently in different people.”

One of the major genetic pathways is APOE ε4, a genetic variant responsible for encoding cholesterol-carrying proteins in the brain. Having one copy of the gene puts people over 65 at risk, while having two copies is the strongest risk factor for the future development of Alzheimer’s disease in that age group.

But she is not a Muslim. Some people with APOE ε4 do not go on to develop Alzheimer’s disease, while others without the gene may find themselves with the characteristic signs of tau tangles and beta-amyloid plaques.

Another pathway to Alzheimer’s disease is inflammation, Freer said, “which is common to all chronic diseases.” Several new genes discovered this year appear to play a role in how the body’s immune system removes damaged cells from the brain.

boost in financing

To advance the research, US federal funding for Alzheimer’s research has increased sevenfold since 2011 to more than $3.4 billion annually, said Rebecca Edelmayer, senior director of scientific engagement at the Alzheimer’s Association.

One focus of the research is finding treatments that target the immune system as well as inflammation in the brain, Edelmayer said, while other research looks at cell metabolism and how cells use energy.

Scientists are also trying to understand more about how brain cells communicate and communicate through synapses, she said, and “we’re seeing investigations looking at gut-brain connectivity, which is another interesting approach.”

Edelmayer added that researchers are racing to find breakthroughs in the treatment, with the help of additional funding in recent years from the public and private sectors. 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 will be culturally appropriate but also effective and scalable around the world,” Edelmayer said.

Search for existing medicines

Another focus of the research is examining existing drugs that may prevent Alzheimer’s disease from taking root in the brain.

In his lab, Harvard’s Tanzi uses tiny organoids made up of human brain cells that can develop the typical amyloid plaques and tau tangles of Alzheimer’s disease in just over a month. Tanzi and Harvard University co-researchers Doo Yeon Kim and Se Hoon Choi published a background paper on their discovery in 2014, calling it “Alzheimer’s in a Dish.”
42 previously unknown genes for Alzheimer's disease discovered

Tanzi and his team spent seven years testing drugs already approved by the US Food and Drug Administration on the “brain” in the dish. Because the Food and Drug Administration has already verified the safety of these drugs, he said, finding a candidate from that group would speed up federal approval of the Alzheimer’s drug, and thus get treatment to patients faster.

Tanzi also tested natural products, such as herbs, spices, vitamins, minerals and antioxidants, for their ability to affect the plaque and tangles in the formation of his mini-brains.

“We were able to quickly screen every approved drug and over 1,000 natural products,” Tanzi said. “And now we have more than 150 specific drugs and natural products that can be tested in clinical trials to hit plaques, tangles, or neuroinflammation.”

Most people don't know these possible signs of early Alzheimer's disease
He and his team at the MassGeneral Institute of Neurodegenerative Diseases in Boston hope to soon begin clinical trials and collaborate with other scientists to see which potential candidates can deliver results.

“It’s all about hitting the right person with the right drug, at the right time while they’re sick,” he told CNN.

“Many people may not know this, but after 40 years, almost all of us have started to build the initial pathology of Alzheimer’s disease, which is amyloid plaque in the brain and neurofibrillary tangles.” “It’s part of life, just as most of us start to form little plaques in our arteries from cholesterol.”

In fact, Tanzi estimates that roughly 30 to 40 million Americans have enough amyloid in their brains right now to take advantage of a drug to lower it — if science has the power to do so safely and affordably.

“I like to say that amyloid is like a matchstick, and tangles are like wildfires that spread and spread for decades,” Tanzi said. “And all the way the big wildfires are causing this, this is neuroinflammation.”

He added that by the time anyone shows any signs of cognitive decline, the “neuritis forest fire is burning,” and it is too late to significantly save the brain and improve thinking and memory skills.

“The elephant in the room is that we wait for the brain to degenerate to the point of dysfunction before we treat this disease,” Tanzi said. “It’s like saying wait until you’ve lost half of the beta cells in your pancreas before we diagnose diabetes.”

One reason clinical trials of drugs over the past few decades have failed to control amyloid buildup is that many of the study participants were in more advanced stages of the disease when “a lot of destruction was done,” Edelmayer said.

“Removing the amyloid at that time wasn’t necessarily helpful,” she said. “It took us some time to really understand at what stage of the disease process we need to specifically target amyloid with drugs.”

Medicare limits coverage of controversial Alzheimer's drug to those in clinical trials
Case in point: the controversial amyloid-clearing drug aducanumab, sold under the brand name Aduhelm, Only tested on people with mild cognitive impairment. The US Food and Drug Administration approved the use of aducanumab in 2021 despite the fact that all but one of the members of the independent expert panel tasked with reviewing the drug’s efficacy voted against approving it.
While aducanumab removed amyloid, the clinical trial showed a slight improvement in cognition in one subgroup of patients. Some doctors and medical institutions across the country have decided not to offer aducanumab to their patients after balancing the drug’s poor performance with significant cost and side effects.
In April, Medicare announced that it would only cover the drug’s $56,000 per year cost if the person was enrolled in a study approved by the Centers for Medicare and Medicaid Services. That same month, Biogen, the company that developed the drug, abandoned the drug’s approval in the European Union. By May, the company announced that it would stop subsidizing the drug.
“I want to show people that to end Alzheimer’s, we need early detection and early intervention about 10 or 20 years before symptoms appear,” Tanzi said. “And what about the 6 million people in this country who have this disease right now? For them, we need to put out the fire, stop the neuroinflammation, stop killing neurons.”

lifestyle interventions

Alzheimer’s disease screening tools will accelerate research and help clinicians detect Alzheimer’s disease at an early stage. However, most current tests are invasive, such as spinal taps, or expensive, such as PET scans, or PET scans, which insurance companies often refuse to cover.

The study found that women responded better than men to early intervention for Alzheimer's disease

“Ultimately, we need screening tools that will be scalable, not invasive, and certainly something cost-effective for patients and their families,” Edelmayer said. “A blood test is really the holy grail if we can make it through. We’re not there yet, but we’re getting close. Ask me in another two years.”

Preventive methods are a central focus of much of today’s research. Lifestyle changes, such as improving exercise, eating a plant-based diet, addressing a lack of sleep, reducing stress, improving social connections and participation, and some types of cognitive training, show great results for people early in the disease process. Keeping cholesterol and blood sugar under control at early ages is also key to good brain health.
Two recent studies in the United States showed that such lifestyle interventions, along with medications, vitamins, and nutritional supplements, can prevent deterioration and also improve memory and thinking skills.

“There were indeed cognitive improvements at 18 months of age in both women and men when compared to the control group,” said Isaacson, who authored the studies. He said that even people who carry the Alzheimer’s gene APOE-4, which increases the risk of dementia in late life, have seen cognitive benefits.

Edelmayer said more than 25 countries are conducting similar cross-cutting lifestyle interventions as part of the World Wide Finger Network. FINGER stands for Finnish Aging Intervention Study for the Prevention of Cognitive Impairment and Disability. People who participated improved their cognition by 25% over two years, according to the study.

“I’m very wary of using words like therapy,” Isaacson said. “But when we use all of these different tools early on, during the pre-dementia years, I think prevention is cure. And hopefully, reducing the risk will delay the pathology long enough that the person dies from something else before they develop mental illness.”

All of these research approaches, Edelmayer said, “put us on the threshold of a new, transformative era in Alzheimer’s disease research.” “Now is the time to confront us, especially for those who are currently living with the disease.”

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