Alzheimer’s disease is a devastating illness that, for decades, didn’t have any effective treatment. Now, there is new hope thanks to the use of monoclonal antibodies that have been shown to slow the progression of Alzheimer’s.
Two medications were approved by the Food and Drug Administration (FDA) in 2023 and 2024: lecanemab (Leqembi) and donanemab (Kisunla).
“This is the first disease-modifying therapy for Alzheimer’s disease,” says UNC Health neurologist Hannah Noah, MD, MPH. “The oral medications currently given for Alzheimer’s disease may give a boost in thinking and memory, but they don’t target the progression of the disease the way this therapy does.”
While a new medication for this disease is extremely exciting, Dr. Noah says it’s important to be realistic about the benefit.
“I don’t oversell these medications, because it’s not a cure,” she says. “These medications slow the progression of Alzheimer’s disease, but they don’t stop it. In trials, these meds have shown about a 30 percent slowing of symptoms in 18 months.”
For someone who is eager to do everything they can to slow the progression of Alzheimer’s disease, that effect may be worth it. Dr. Noah answers questions about how these drugs work and who is a good candidate for treatment.
How do monoclonal antibodies work for Alzheimer’s disease?
Monoclonal antibodies are not new; they were first approved by the FDA in 1986 as a treatment to prevent kidney transplant rejection. These lab-made proteins have one job: to bind to a specific kind of cell in the body. In the past 40 years, the FDA has approved more than a hundred monoclonal antibody treatments for conditions including cancer, autoimmune disease, osteoporosis and infectious diseases.
In the case of Alzheimer’s disease, these monoclonal antibodies target and remove the amyloid plaques that form between neurons in the brain. Amyloid plaques disrupt communication between neurons and affect how a person with Alzheimer’s thinks.
Amyloids are created by proteins that have “misfolded,” or changed their shape, so that they can no longer do the things they are supposed to do in the body; when they clump together into plaques, they can cause problems. In Alzheimer’s disease, the amyloid plaques are made up of the protein amyloid beta.
Lecanemab is given through an IV infusion every two weeks, while donanemab is given through an IV every four weeks. A typical treatment lasts about an hour.
“We give these drugs for 18 months, and in that time, they clear out the amyloid,” Dr. Noah says. “In many cases, the amyloid will be completely gone.”
While the monoclonal antibodies can remove existing amyloid, they can’t reverse any damage that amyloid plaques may have already caused, and amyloid will slowly grow back. There is no treatment to address the tangles of the protein tau, which form inside the neurons and cause cell death in the brain, leading to further cognitive decline. It’s for these reasons that monoclonal antibodies are not considered a cure.
Still, this advancement in modifying disease progression is leading to additional work that provides hope, Dr. Noah says.
“People can have a buildup of amyloid a decade before they experience any memory symptoms,” Dr. Noah says. “One question being investigated is, if someone has a known amyloid buildup but no symptoms yet, could we go ahead and treat and prevent disease? We expect results from a trial on that question in the next few years.”
What are the risks of monoclonal antibodies for Alzheimer’s disease?
The FDA approved lecanemab and donanemab with an important safety warning about the risk of amyloid-related imaging abnormalities, or ARIA.
“These are small areas of bleeding and swelling on the brain” that can be seen on MRI, Dr. Noah says. “It’s thought that these medications can make the blood vessels in the brain leaky.”
About 1 in 4 patients experienced some degree of ARIA in clinical trials. “But in our experience, the ARIA rate has been lower,” Dr. Noah says. “Most often, it’s very minor and asymptomatic.”
If you are prescribed these medications, you will have four MRIs in the first six months to check for signs of ARIA.
“Depending on how severe the bleeding or swelling is, we can pause, stop or keep going with the treatment,” Dr. Noah says.
In some cases, the bleeds can be severe enough to cause symptoms, most commonly headache, confusion and vision changes; very rarely, they can cause seizures and even be fatal.
If you’re prescribed a monoclonal antibody for Alzheimer’s treatment, your doctor will talk to you about the symptoms of a brain bleed and when to get help, Dr. Noah says. Alzheimer’s medications with a lower risk of ARIA are also being researched.
Monoclonal antibody treatments may cause infusion reactions, or symptoms that appear soon after receiving the medicines. These include headache, body pain and fatigue; Dr. Noah says these symptoms typically clear up in a day, and medications are available to help manage them.
Who is a good candidate for monoclonal antibodies for Alzheimer’s disease?
Before you receive treatment with monoclonal antibodies, you must have a confirmed diagnosis of Alzheimer’s disease. The presence of amyloid plaques can be detected via a special PET scan of the brain or a spinal tap to test the cerebrospinal fluid. Absent amyloid plaques, there is no reason to do the treatment.
“It’s ideal if Alzheimer’s disease is the main driver of cognitive symptoms,” Dr. Noah says, noting that some people may have two factors driving their symptoms, such as Alzheimer’s and vascular disease dementia. “This treatment also works best if it’s earlier in the disease, when a person just has mild cognitive impairment or mild dementia.”
When a person is earlier in the disease, there is less damage from the amyloid plaques that can’t be reversed. When the disease has progressed, the benefit is no longer significant.
Because of the risk of ARIA, people with a history of bleeding issues or people who take blood thinners may not be good candidates. People with a certain gene variant called APOE4, which is a genetic risk factor for Alzheimer’s disease, are at an increased risk of ARIA. Dr. Noah says guidelines may vary from center to center as to whether people with these risks can receive anti-amyloid monoclonal antibodies.
Lastly, if you are considering this therapy, you should be aware of the time involved; you must regularly visit an infusion center for 18 months and be available for regular MRIs.
If you’re concerned about the symptoms of dementia, talk to your doctor. If you need a doctor, find one near you.