5 Reasons We Don’t Have a Cure for Alzheimer’s Disease

It’s hard to cure a disease when its cause is still up for debate

Bethany Brookshire

Reviewed by

Howard Fillit, M.D.

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En español

Published January 17, 2024

An illustration of nerve cells affected by Alzheimer's disease

KATERYNA KON/SCIENCE PHOTO LIBRARY / Getty Images

When the Food and Drug Administration gave its full approval in July for a new Alzheimer’s drug, there was great buzz among scientists and the media. Alzheimer’s Association CEO Joanna Pike called it “a tremendous step forward.” But while the medication, known as Leqembi, slows mental decline — by about five months in some patients who have early stage disease — it doesn’t repair the damage in the brain or stop the disease from ever progressing. There are also risks involved with its use.

The excitement comes from the fact that finally, after two decades of effort, there’s at least one drug available to slow the disease. It’s been a long slog with many failures along the way to get to this milestone. Researchers have faced a slew of difficulties in coming up with treatments for Alzheimer’s disease, which affects more than 6 million people in the United States, 55 million worldwide, according to the Alzheimer’s Association.

Some of the challenges in developing drugs for Alzheimer’s and other causes of dementia apply to any drug aimed at the human brain. Others are specific to the unique hurdles surrounding Alzheimer’s disease.

1. Scientists aren’t sure what causes Alzheimer’s disease.

Some firmly believe that Alzheimer’s is primarily caused by what’s known as amyloid plaques. These occur when a protein in the brain breaks down incorrectly into clumps. Those toxic clumps form sticky collections between nerve cells, stopping the cells from functioning as they should. But others are not convinced.

One problem is that the amount of amyloid plaques in a person’s brain doesn’t correspond to whether they show signs of dementia, says neurologist Alberto Espay, M.D., at the University of Cincinnati. By the age of 85, he says, “Sixty percent of us have this in our brains.” Yet many fewer, under a third of people 85 and older, will have dementia, according to the National Institute on Aging.

Another problem: Those antibody drugs, including Leqembi, that clear away amyloid plaques only have small effects on the dementia itself. That’s what makes Lon Schneider, M.D., skeptical. The effects are statistically significant, with patients receiving the drugs showing less decline in cognition than people who got a placebo, says Schneider, who studies Alzheimer’s disease at the University of Southern California Keck School of Medicine. But the size of the difference is so small that many patients and their caregivers might not be able to detect it.

Just because these drugs haven’t shown miraculous effects, the beta amyloid plaques could still be the cause, says psychiatrist Clive Ballard, M.D., who studies cognitive health and dementia at the University of Exeter in England. It may be that the antibody drugs have simply failed so far to clear the right plaques, or clear them from the right places.

2. Most drugs fail during testing.

Getting a new drug from the lab to the pharmacy is a long and costly process. In fact, for all the drugs that make it into human testing, more than 90 percent never get any further, according to the U.S. Congressional Budget Office. The number of drugs for dementia that fail “might be a little bit higher” than average, Ballard says. But “it’s not radically different.” What is different is that there are very few clinical trials for dementia at all. “If you only have 50 trials, you’re touch-and-go whether you’re going to get one compound out of that,” he says. As of January 2023, 141 drugs were being tested in patients for the treatment of Alzheimer’s disease, researchers reported in May 2023 in Translational Research & Clinical Interventions.

3. Brains are almost impenetrable.

The human brain is protected by the blood-brain barrier, a layer of cells separating the brain from harmful things in the blood. Imagine a security guard letting oxygen and important hormones in, but blocking bacteria, viruses and toxins from reaching the delicate cells of the brain. Unfortunately, that barrier shuts out a lot of potentially helpful drugs, too. “Your immediate problem is that only 20 percent of the compounds … cross the blood-brain barrier,” Ballard says. Scientists are testing some clever workarounds, attaching the drugs to nanoparticles or tucking them inside little water-friendly packages called hydrogels to smuggle the drugs past the brain’s security system.

4. Treating a symptom isn’t treating a disease.

Most of the medications for people with Alzheimer’s aim at the symptoms, not the cause of the disease. Once diagnosed with dementia, a patient may receive drugs like a cholinesterase inhibitor or memantine to adjust levels of some brain chemicals and ease some problems.

“You give a patient something that helps his symptoms,” Espay says. But that’s a bit like taking Tylenol because you have the flu and a fever. The drug brings the fever down and makes you more comfortable. But the fever is just a symptom; you still have the flu.

It’s no small thing to treat those symptoms, Ballard points out. For people with moderate dementia, “I think the maintenance of function is perhaps most important,” he says. It’s “the difference between, say, being able to walk a few steps independently and needing a hoist to be moved. That’s a huge impact on independence and quality of life.”

The recently approved Leqembi and other antibody drugs still being tested, however, go after the cause of the disease. These drugs bind to and clear away the sticky amyloid plaques. If those plaques are the cause of Alzheimer’s disease, scientists could be on to something.

But there’s probably more involved in this disease. So, researchers are pursuing many potential players in the disease, such as inflammation and microglia — small cells that are a kind of clean-up crew in the brain. Some studies are even targeting circadian rhythms (the body’s internal clock) or hormones like estrogen that might play a role in the disease.

5. There’s not a lot of funding for Alzheimer’s research.

Part of the problem comes back to the lack of clarity on the cause of Alzheimer’s and the steep costs of developing a single drug. Ballard says it’s also a problem that there’s less awareness around dementia — and less hope.

“People are now beginning to become aware of [dementia], but they still see it as a death sentence,” he says. “The more you have hope and the more treatments potentially can do something, the easier it is to persuade people to invest in it.”

The U.S. government will spend about $3.7 billion on Alzheimer’s and dementia research in 2023, according to the National Institutes of Health. This is a big increase from 2015, when the federal government funded $631 million in research. But it’s also not much more than the $3.3 billion that will be spent on HIV/AIDS. Around 119,000 people died from Alzheimer’s disease in 2022. Compare that to the 18,000 people diagnosed with HIV that died of any cause in 2020, the latest year data is available. Because of a lot of research and funding, many people are living long, healthy lives with HIV. With more funding and research for Alzheimer’s disease, some day it might, like HIV, go from a death sentence to a manageable condition.

The new antibody treatments have Ballard feeling optimistic. “We’re starting to get some treatments that start looking like [they have] benefit,” he says. While the trials are limited, and focus on people with early disease, any small success gives people hope. Hope, he adds, sparks more research, and eventually, more treatments.

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Bethany Brookshire is a science writer with a Ph.D. in physiology and pharmacology, and author of the 2022 book Pests: How Humans Create Animal Villains.

Howard Fillit, M.D., is cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation.