What role do amyloids play in Alzheimer’s disease?

“More than a century ago, Dr. Alois Alzheimer described the brain changes in a younger woman who had passed away from what we now call Alzheimer's disease,” explains neurologist Dan Murman, MD. “The hallmark changes were amyloid plaques and neurofibrillary tangles. That's been the focus of Alzheimer’s research ever since.”

Amyloid is an aggregation of a protein called beta-amyloid that accumulates in the brain of older adults. It's one of the hallmark brain changes in Alzheimer's disease. ​​Scientists don’t know precisely what role amyloids play in Alzheimer’s disease. It appears that amyloids may be damaging or toxic to nerve cells.

Amyloid levels aren’t a good indicator of the severity of memory loss or the stage of Alzheimer’s disease. However, they seem to be an important marker of the start of the disease process. The buildup of amyloid begins about 15 years before people have memory loss. By the time memory loss occurs, the amount of amyloid in the brain is fairly high and doesn't change much after that.

How does anti-amyloid therapy work?

Anti-amyloid treatments work by attaching to and removing beta-amyloid, a protein that accumulates into plaques, from the brain. Each drug works differently and targets beta-amyloid at a different stage of plaque formation.

The drugs haven’t been shown to stop progression or to help people improve cognitive function. However, by removing the amyloid plaque, these drugs appear to slow down brain changes in the early stages of Alzheimer’s disease and slow the rate of decline on tests of thinking and everyday function by approximately 30% in the 1 ½-year trials.

“It’s possible that the benefit of anti-amyloid therapy may grow over time,” says Dr. Murman. “Some studies suggest that it might keep people at these mild stages of the disease for several years longer. But we still need more information to prove that.”

Aducanumab

The anti-amyloid antibody drug aducanumab (Aduhelm®) was the first drug in this class to receive accelerated Food and Drug Administration approval based on its ability to remove amyloid plaques, as seen on a brain scan. This therapy was studied in people with mild cognitive impairment or mild dementia due to Alzheimer's disease who also have evidence of a buildup of amyloid plaques in the brain. This drug is administered monthly by infusion.

Lecanemab

Lecanemab (Leqembi™) is an anti-amyloid antibody intravenous infusion therapy with accelerated FDA approval for treatment of early Alzheimer's with confirmation of elevated beta-amyloid. It works by attaching to and removing beta-amyloid in the brain. This drug is approved for people with early Alzheimer's disease. Candidates for this treatment should also have confirmation of elevated beta-amyloid plaques in the brain. This drug is given every two weeks by infusion.

Donanemab

Donanemab is a biological drug in trial to treat early symptoms of Alzheimer's disease. It has shown positive results in a previously reported phase 2 trial. Like the other treatments, it works by removing beta-amyloid in the brain. It is given to patients through monthly infusion therapy.

Currently, none of these medications are covered by Medicare, Medicaid or private insurance. However, if one or more of these drugs receive full FDA approval, insurance carriers will reconsider coverage at that time. You should talk with your doctor to develop a treatment plan right for you, including weighing the benefits and risks of all approved therapies.

Who is a candidate for anti-amyloid treatments?

The new anti-amyloid drugs are approved for two groups of people: those with mild cognitive impairment and those with mild dementia due to Alzheimer’s disease. Recent trials suggest that removing amyloid slows the decline in memory tests and in everyday function.

As people progress into the later stages of dementia, some of these brain changes continue with or without the presence of amyloid plaque. This means that removing the amyloid won't help patients at a more advanced stage of the disease. Those patients will continue progressing without much change, even if amyloids are removed.

What are the risks? Is there anyone who should not use these drugs?

The most commonly reported severe side effects of anti-amyloid therapies have been infusion-related reactions and amyloid-related imaging abnormalities. This common side effect that does not usually cause symptoms but can be serious. It’s typically microscopic bleeding on a brain scan or temporary swelling in areas of the brain that usually resolves over time.

To begin these treatments, a patient must be able to tolerate brain MRI scans. So, a person who’s claustrophobic or who has a pacemaker would not be a candidate for this treatment. This is because anti-amyloid treatment requires periodic MRI scans to check for microscopic bleeding or swelling as a result of treatment.

Patients also can’t be on strong blood thinners like Coumadin® or Eliquis® because of the increased risk of bleeding. Patients will need biomarker confirmation of amyloid plaque pathology before starting one of these drugs. This can be done by an amyloid PET scan or testing spinal fluid obtained by lumbar puncture, which is currently not covered by insurance.

Where do I go if I’m interested in the new anti-amyloid treatments?

Currently, anti-amyloid therapy is only available to patients participating in a clinical trial. If a drug receives full-FDA approval, Medicare and other insurers may begin covering the cost of treatment. It is uncertain when this will happen, but some expect at least one of these drugs to receive full-FDA approval in 2023.

Nebraska Medicine providers in neurology, geriatric medicine and geriatric psychiatry can discuss options with patients who may be eligible for this treatment. Call 800.922.0000 to schedule an appointment.