"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, but 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 significant memory loss occurs, the amount of amyloid in the brain is high but doesn't change much after that. 

How anti-amyloid therapy works 

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% to 40% in the 1½-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 one to two years longer. But we still need more information to prove that." 

Currently approved treatments 

Lecanemab (Leqembi™) 

Lecanemab was approved by the FDA in July 2023. It is an anti-amyloid antibody for treatment of prodromal (the earliest stage) to mild Alzheimer's with confirmation of elevated beta-amyloid through an amyloid PET scan. Treatment consists of IV infusions every two weeks. A baseline MRI is required before starting treatment, followed by three safety MRIs within the first six months. Treatment typically continues for 2-3 years until a patient progresses to a moderate stage of dementia. 

Donanemab (Kisunla™) 

Donanemab was approved by the FDA in July 2024. Like lecanemab, it is an anti-amyloid antibody for treatment of prodromal to mild Alzheimer's, requiring confirmation of elevated beta-amyloid through an amyloid PET scan. Treatment consists of monthly IV infusions. A baseline MRI is required, followed by four safety MRIs within the first eight months. Unlike lecanemab, patients can stop donanemab infusions after confirming clearance of amyloid through a follow-up PET scan. Most patients achieve this clearance and can stop treatment after about one and a half years. 

Both drugs are covered by Medicare, Medicaid and some private insurance plans. 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 can receive anti-amyloid treatments? 

The anti-amyloid drugs are approved for two groups of people:

• Those with mild cognitive impairment: These patients have measurable declines in memory and thinking but remain independent in their everyday activities.
• Those with mild dementia due to Alzheimer's disease: These individuals experience memory loss and may have trouble with complicated activities but can typically still drive, manage medications, handle finances and perform most daily activities with minimal assistance.

These drugs are ineffective for patients at a moderate or advanced stage of dementia. In later stages, brain changes occur regardless of amyloid plaque presence, so removing amyloid does not benefit advanced-stage patients. These patients will continue to progress without significant change, even if amyloid plaques are removed. 

Treatment risks and safety  

The most reported side effects of anti-amyloid therapies have been amyloid-related imaging abnormalities, or ARIA. ARIA consists of either areas of microscopic bleeding or swelling in the brain that can be detected through MRI. Around 15% to 25% of patients receiving anti-amyloid therapy will develop ARIA, though more than 90% of these cases are asymptomatic. Between 2% to 3% of patients can have serious side effects with ARIA. 

Important safety considerations include:

• Patients must be able to tolerate brain MRI scans (excluding those who are claustrophobic or have pacemakers).
• Treatment is not suitable for patients on strong blood thinners like Coumadin® or Eliquis® due to increased bleeding risk.
• All patients require confirmation of amyloid plaque pathology through an amyloid PET scan before starting treatment.

How to get started 

Nebraska Medicine is one of the few providers in the region offering the currently approved anti-amyloid therapy. Referring physicians can work up patients and then refer to the Dementia and Memory Disorders Clinic.  

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.