The Fight Against Alzheimer’s Disease: Where Are We Now?

“It was the summer of ’86. I was 27 years old,” Tanzi recalled. “I remember thinking that for the first time since Dr. Alois Alzheimer described amyloid in 1906, we knew its origin.”

The discoveries never stopped. Scientists around the world continue to unravel the genetic basis of this heartbreaking disease that steals the mind and leaves the body empty.

Many pathways lead to Alzheimer’s disease

Because there are many genes that contribute to the development of Alzheimer’s disease and other types of dementia, scientists believe that each person’s journey may be different.

“There’s a saying: When you see someone with Alzheimer’s, you’ve seen someone with Alzheimer’s,” says Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Florida Atlantic University Schmidt College of Medicine’s Center for Brain Health.

“Alzheimer’s disease is a multifactorial disease, consisting of different pathologies, and each person has their own path. The disease presents and progresses differently in different people.”

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

But this is not a given. Some people with APOE ε4 do not develop Alzheimer’s disease, while others who do not have the gene may show specific symptoms of tau tangles and beta amyloid 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 removes damaged cells from the brain.

Increased funding

To boost research, U.S. federal funding for Alzheimer’s research has increased sevenfold since 2011, to more than $3.4 billion annually, said Rebecca Edelmeier, senior director of research at the Alzheimer’s Association.

One area of ​​research is finding therapies that target the immune system as well as inflammation in the brain, while other research studies cellular metabolism and how cells use energy.

Scientists are also trying to understand more about how brain cells connect and communicate through synapses, and “We’re seeing research looking at gut-brain communication, which is another interesting approach,” he said.

Researchers have been racing to find breakthroughs in treatments in recent years with the help of additional funding from the public and private sectors, Edelmeier added. The Chicago-based Alzheimer’s Association alone has donated more than $300 million to fund more than 920 projects in 45 countries.

“We want to focus on strategies that are culturally appropriate, but effective and scalable globally,” Edelmeier said.

Search for current medications

Another area of ​​research is investigating existing drugs that prevent Alzheimer’s from taking root in the brain.

In his lab, Harvard’s Tanzi uses tiny organoids of human brain cells that can develop the amyloid plaques and tau tangles typical of Alzheimer’s disease in just over a month. Tanzi and Harvard co-authors Doo Yong Kim and Se Hoon Choi published a seminal paper about their discovery in 2014, which they called “Alzheimer’s in Food.”
42 previously unknown genes for Alzheimer's disease have been discovered

Tanzi and his team spent seven years testing drugs that the U.S. Food and Drug Administration had already approved for the “brain” in the pot. As the FDA reviews the safety of those drugs, finding a candidate in that group could speed up federal approval for Alzheimer’s disease and help patients get treatment more quickly, he said.

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

“We were able to rapidly screen every approved drug and over 1,000 natural products,” Tanzi said. “And now we have more than 150 identified drugs and natural products that can be tested in clinical trials to fight plaque, wrinkles or neuroinflammation.”

Many people are unaware of the early signs of Alzheimer's
He and his team at the MassGeneral Institute of Neurodegenerative Diseases in Boston hope to start clinical trials soon and collaborate with other scientists to see which of the potential candidates might work.

“It’s all about getting the right person with the right drug at the right time during their illness,” he told CNN.

“Many people may not be aware of this, but after age 40, we all begin to develop Alzheimer’s initiator pathology, which is amyloid plaques and neurofibrillary tangles in the brain,” he continued. “It’s part of our lives that most of us start to build up some plaque in our arteries from cholesterol.”

In fact, Tanzi estimates that about 30 million to 40 million Americans have enough amyloid in their brains to benefit from a drug to lower it if science can do it safely and affordably.

“I like to say that amyloid is like a match, and the tangles are like a brush fire that spreads over decades,” Tanzi said. “You’re starting big wildfires down the road, which is neuroinflammation.”

By the time a person shows any signs of cognitive decline, he added, “the forest fire of neurospasm is raging,” and it’s too late to significantly save the brain and improve thinking and memory skills.

“The elephant in the room is that we wait until the brain is dysfunctional before we treat it,” Tanzi said. “It’s like saying wait until you’ve lost half the beta cells in your pancreas before we diagnose diabetes.”

According to Edelmeier, one of the reasons clinical drug trials over the past few decades have failed to control amyloid accumulation is that most of the study participants had advanced disease because “too much destruction was done.”

“At that time, removing the amyloid wasn’t necessarily beneficial,” he said. “It took us a while to figure out where in the disease process we needed to specifically target amyloid with drugs.”

Medicare limits coverage of controversial Alzheimer's drug in clinical trials
For example: the controversial amyloid-busting drug aducanumab, sold under the brand name Aduhelm, tested only in people with mild cognitive impairment. The FDA approved the use of aducanumab in 2021, but all but one member of an independent expert panel voted against reviewing the drug’s effectiveness.
Although aducanumab removed the amyloid, the clinical trial showed a small improvement in cognition in a subset of patients. Some doctors and medical facilities across the country have decided not to offer aducanumab to their patients after weighing the drug’s poor efficacy against its cost and serious side effects.
In April, Medicare announced it would cover $56,000 a year in drug costs if a person enrolled in a study approved by the Centers for Medicare & Medicaid Services. In the same month, Biogen, the company that developed the drug, refused to get approval for the drug in the European Union. By May, the company announced it would stop supporting the drug.
“I want to make it clear to people that to reverse Alzheimer’s, we need early detection, early intervention 10, 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 neuron inflammation, stop the neurons from being killed.”

life intervention

Alzheimer’s screening tools accelerate research and help clinicians detect Alzheimer’s disease earlier. However, many current tests are either invasive, such as spinal taps, or too expensive, such as positron emission tomography or PET scans, which insurance companies often refuse to cover.

Research shows that women respond better than men to early Alzheimer's intervention

“Ultimately, we need screening tools that are scalable, noninvasive, and cost-effective for patients and their families,” Edelmeier said. “The blood test is really the holy grail if we’re ever going to get there. We’re not there yet, but we’re getting closer. Ask in two years.”

Preventive methods are the main focus of today’s research. Lifestyle changes such as increasing exercise, eating a plant-based diet, eliminating sleep deprivation, reducing stress, improving social connections and engagement, and some types of cognitive training have shown impressive results for people early in the course of the disease. Controlling cholesterol and blood sugar at an early age is also key to brain health.
Two recent US studies show that such lifestyle interventions, along with medications, vitamins and supplements, can prevent decline and improve memory and thinking skills.

“In fact, at 18 months, both women and men showed cognitive improvement,” said Isaacson, the study’s lead author. Even people who carry the Alzheimer’s APOE ε4 gene, which increases the risk of dementia, saw cognitive benefits, he said.

More than 25 countries are implementing such a multidomain lifestyle as part of the World Wide FINGER network, Edelmeier said. FINGER stands for Finnish Geriatric Intervention Study for the Prevention of Cognitive Impairment and Disability. According to research, people have improved their cognitive abilities by 25% within two years.

“I’m very careful about using words like cure,” Isaacson said. “But if we use all these different tools early, before dementia, I think prevention is the cure. And hopefully reducing the risks will delay the pathology long enough that the person will go through it before they go on to something else. Dementia.”

All of these research methods “bring us to the brink of a transformative new era in Alzheimer’s research,” Edelmeier said. “Now is the time for us to stand up, especially for those currently living with the disease.”

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