What are anti-amyloid antibodies, and how do they work?

Anti-amyloid antibodies are a class of monoclonal antibody drugs designed to remove amyloid-beta — a protein that accumulates abnormally in the brains of people with Alzheimer's disease. Two such drugs have full FDA approval as of 2026: lecanemab and donanemab.

What problem they target

For decades, the leading explanation for what causes Alzheimer's has been the amyloid hypothesis: that the abnormal accumulation of amyloid-beta in the brain triggers a cascade of damage including tau pathology, neuronal loss, and cognitive decline. The amyloid hypothesis is not the whole story of Alzheimer's, and it has been the subject of legitimate scientific debate. But amyloid is the first molecular target for which therapies have demonstrated clinical disease-modifying effect.

How they work

Anti-amyloid antibodies bind to amyloid-beta in the brain, recruiting the immune system to clear it. Different antibodies in this class target different forms of amyloid — soluble protofibrils, fibrillar deposits — and the differences matter for both efficacy and side-effect profile.

What the trials showed

The pivotal trials demonstrated that these drugs slow the rate of clinical decline in people with early symptomatic Alzheimer's by a clinically meaningful but not transformative amount — typically described as roughly 25 to 35 percent slowing on standard cognitive and functional measures over 18 months of treatment. This is not the same as stopping the disease, and it is not the same as restoring lost function. It is slowing the rate at which the disease gets worse.

What the side effects look like

The defining safety consideration is amyloid-related imaging abnormalities, or ARIA — small areas of brain swelling or microbleeding visible on MRI. Most ARIA cases are mild and asymptomatic; a minority are clinically significant. ARIA risk is meaningfully higher in people who carry two copies of the APOE4 gene variant. This is why APOE genotyping is now standard before initiating therapy and why on-treatment MRI surveillance is required.

Who is eligible

Eligibility is restricted to people with mild cognitive impairment or mild Alzheimer's dementia, with confirmed amyloid pathology, no significant contraindicating findings on baseline MRI, and no medications or conditions that materially increase bleeding risk. People with more advanced disease are not currently eligible — the trials enrolled early-disease populations and the drugs have not been studied in later stages.

What is changing

The two most material near-term changes are: subcutaneous formulations that would replace the IV infusion with a self-administered injection, and ongoing learning about how to stratify treatment by APOE genotype. Both are discussed in our Signals.