People are living longer and longer lives these days, but sadly, that also means more people are living with -- and dying from -- Alzheimer's disease (AD), which is marked by a serious decline in mental ability. According to the Alzheimer's Association, there are more than 5 million people in the United States with Alzheimer's. That number is expected to nearly triple by 2050.

There's no cure for the disease, which is the sixth leading cause of death in the United States. Pharmaceutical companies are exploring ways to slow the condition's progress, treat its symptoms, and better diagnose it. One report notes that sales of Alzheimer's medications hit $3.5 billion in 2018 and are expected to have a 7.2% compound annual growth rate through 2030.

According to the Alzheimer's Association, a healthy brain has 100 billion nerve cells, or neurons. The brain has certain proteins, known as beta-amyloid and tau proteins, that help stabilize the nerve cells. However, in Alzheimer's patients, when fragments, or plaques, of beta-amyloid and misshapen or tangled tau proteins build up, they may hinder communication between neurons and contribute to cell death by keeping key nutrients from repairing neurons.

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Many Alzheimer's drugs in trials are attempting to stop plaques from forming in the brain. Others hope to alleviate the symptoms of the condition. And still others are intended to serve as biomarkers for the plaques to help detect the disease earlier.

Eli Lilly (NYSE:LLY), Axsome Therapeutics (NASDAQ:AXSM), and Biogen (NASDAQ:BIIB) all have promising drugs for the treatment or detection of Alzheimer's. 

Eli Lilly has been working on the problem for a while

Eli Lilly has sponsored more than 70 studies on Alzheimer's disease and mild cognitive impairment (MCI). Since there's no cure, any positive or negative news regarding a drug for the disease moves the needle, even for a company as large as Lilly.

In 2016, the Indianapolis-based company's stock dropped more than 10% in one day when Alzheimer's candidate solanezumab failed its phase 3 trial because it did not slow cognitive decline in subjects.

Undeterred, Lilly got good news late last month when the U.S. Food and Drug Administration (FDA) gave approval to Tauvid as the first drug to determine the density of tau tangles in the brain. Previously, doctors could only guess at the problem in living patients, as the only method of measuring tau tangles had to be done through postmortem surgery.

Lilly had $22.3 billion in net sales last year (and boasts 35,000 employees), so it has plenty to fall back on if Tauvid isn't a huge moneymaker. Lilly's shares are up more than 23% year to date.

Axsome has a potential treatment for one Alzheimer's symptom

Axsome Therapeutics, a clinical-stage biopharmaceutical company based in New York City, isn't making any revenue yet, but it does have several late-stage candidates -- including one, AXS-05, that it says has the potential to make $1.5 billion to $3 billion a year treating one Alzheimer's symptom.

Axsome's shares are down roughly 25% year to date, but they're up more than 200% over the past 12 months.

The company says AXS-05 could be useful for several conditions, including treating agitation that it says is present in 70% of Alzheimer's patients. AXS-05, which is also in trials for major depressive disorder, treatment-resistant depression, and smoking cessation, just came off a positive phase 2/3 trial for AD agitation. 

"The positive ADVANCE-1 Phase 2/3 trial represents a potentially important milestone for Alzheimer's disease patients, their caregivers, and physicians, particularly given the lack of approved treatments for, and the serious and distressing nature of, Alzheimer's disease agitation," Axsome CEO Herriot Tabuteau said in an April release. "We look forward to discussing these data with the FDA."

The company has another promising drug unrelated to Alzheimer's, AXS-07, for migraines. The company says it hopes to get approval for that indication from the FDA later this year.

Biogen has a lot riding on its Alzheimer's drug

Biogen, which is based in Cambridge, Mass., is facing the loss of patent protection for its multiple sclerosis drug Tecfidera. It's consequently putting a lot of faith in its Alzheimer's drug, aducanumab. 

Tecfidera earned $4.4 billion last year, nearly 40% of the company's total revenue. Last week, however, a court invalidated a key patent for the drug, which means Mylan (NASDAQ:MYL) may be able to come out with a generic version this year. 

Biogen is partnering with Japanese pharmaceutical Eisai (OTC:ESALY) to develop aducanumab. In March 2019, Biogen said that the drug had failed two phase 3 trials. However, last October, the company reversed course, saying that a reanalysis of the study using a larger data set and higher doses of the drug justified an FDA filing. The reassessment showed that 23% of patients saw improvement in cognitive ability compared to placebo in one of the trials.

Management plans to submit the drug again in the third quarter. Obviously, it's still a big question whether the FDA will approve it. But if it does, the treatment would be worth billions, because it would be the first to reduce cognitive decline connected with Alzheimer's.

Choosing the right Alzheimer's investment for you

Lilly is the easy choice because Tauvid will prove important whether or not a cure is ever found for Alzheimer's. Lilly is also a large company with a big stable of drugs, so it's not overly reliant on the success or failure of one medication.  

Of the three, Biogen is the biggest risk-reward candidate. If the company gets approval from the FDA and can bring aducanumab to market, the stock will soar. However, if its application is turned down -- and that's a very real possibility -- you'll be left with a company that is losing patent protection on its top drug.

Axsome is obviously a risky play; there's a lot of work to be done for the company to profit off AXS-05. However, the drug has done quite well in trials and has tremendous upside -- just not as much as there will be for Biogen if its candidate succeeds.

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.