What Dissolves Plaque in the Brain? Understanding Anti-Amyloid Therapies

October 11, 2025 •

5 min read

Over 6 million Americans are affected by Alzheimer's disease, a condition characterized by sticky beta-amyloid plaques that clump together in the brain. Thanks to recent advancements in pharmacology, monoclonal antibody therapies have been developed to target and remove these toxic deposits. This raises the critical question: what dissolves plaque in the brain, and how do these new medications function?

Quick Summary

Anti-amyloid monoclonal antibody therapies, including lecanemab and donanemab, can gradually remove beta-amyloid plaques associated with early Alzheimer's disease. These treatments work by recruiting the immune system and have demonstrated a modest slowing of cognitive decline in qualified patients. Potential risks, including brain swelling and bleeding, require careful medical monitoring.

Key Points

Approved Medications Exist: The FDA has approved monoclonal antibody therapies, like lecanemab and donanemab, that can help dissolve beta-amyloid plaque in the brain for early-stage Alzheimer's.
Slowing, Not Reversing, Decline: These anti-amyloid drugs have demonstrated the ability to slow the rate of cognitive and functional decline, but they do not stop or reverse Alzheimer's disease entirely.
Serious Risk of ARIA: Potential side effects include Amyloid-Related Imaging Abnormalities (ARIA), such as brain swelling or bleeding, which requires routine MRI monitoring.
Early Stage Only: Anti-amyloid therapies are currently indicated only for patients with mild cognitive impairment or early-stage Alzheimer's with confirmed amyloid plaques.
Targeted Mechanisms: Lecanemab works by clearing amyloid protofibrils, while donanemab specifically targets modified amyloid within existing plaques.
Future Research Explores New Paths: Beyond current drugs, research continues into next-generation antibodies, tau-targeting therapies, vaccines, and immune system modulation to combat the disease.

The Amyloid Hypothesis and Brain Plaque Formation

Brain plaque, specifically beta-amyloid plaque, is a defining pathological hallmark of Alzheimer's disease. Amyloid-beta (Aβ) is a protein fragment derived from a larger protein called amyloid precursor protein (APP). In a healthy brain, these fragments are cleared away, but in Alzheimer's disease, they accumulate and clump together to form toxic plaques outside of neurons. This aggregation disrupts communication between brain cells, triggers inflammation, and eventually leads to cell damage and cognitive decline. The amyloid hypothesis, a long-standing theory in Alzheimer's research, posits that this amyloid buildup is a key initiating event in the disease cascade. Targeting and clearing these plaques has become a central focus for developing disease-modifying therapies, rather than simply treating the symptoms.

The Arrival of Anti-Amyloid Monoclonal Antibodies

In a significant breakthrough for Alzheimer's treatment, the U.S. Food and Drug Administration (FDA) has given full approval to new anti-amyloid monoclonal antibody (mAb) therapies. These are lab-made antibodies designed to recognize and bind to the beta-amyloid protein, effectively flagging it for removal by the body's immune system. The approval of these medications, including lecanemab (Leqembi) in 2023 and donanemab (Kisunla) in 2024, marks a new era of therapeutics that can modify the underlying biology of the disease.

How Do Anti-Amyloid Drugs Work?

Monoclonal antibodies are a form of passive immunotherapy. When infused into a patient, the antibodies travel through the bloodstream and cross the blood-brain barrier to bind with beta-amyloid. The precise mechanism can differ slightly between drugs:

Lecanemab (Leqembi): This drug targets and binds specifically to soluble amyloid-beta protofibrils, which are precursors to the full-blown plaques. By neutralizing these smaller, more mobile clusters, lecanemab helps prevent the formation of larger plaques and assists in their clearance.
Donanemab (Kisunla): This therapy targets a modified form of beta-amyloid called N3pG, which is found in established plaques. By attaching to this specific marker, donanemab promotes the removal of existing amyloid plaques from the brain.

By helping the immune system remove these protein aggregates, these drugs aim to slow the progression of brain damage associated with Alzheimer's. Clinical trials have shown that these drugs can reduce amyloid levels in the brain and lead to a modest slowing of cognitive and functional decline in patients with early-stage disease.

Comparison of Approved Anti-Amyloid Therapies


Feature	Lecanemab (Leqembi)	Donanemab (Kisunla)
Mechanism	Targets amyloid-beta protofibrils, preventing plaque formation.	Targets a modified form of amyloid-beta (N3pG) in established plaques.
Administration	Intravenous (IV) infusion every two weeks.	Intravenous (IV) infusion every four weeks.
Treatment Duration	Ongoing treatment, typically continuing for years.	Treatment can be stopped once amyloid clearance is confirmed via a follow-up PET scan.
Primary Goal	Reduces plaques and slows cognitive decline.	Clears plaques and slows cognitive decline.
FDA Approval	Fully approved in July 2023.	Fully approved in July 2024.
Serious Side Effects	Amyloid-Related Imaging Abnormalities (ARIA), including brain swelling (ARIA-E) and bleeding (ARIA-H).	Amyloid-Related Imaging Abnormalities (ARIA), including brain swelling (ARIA-E) and bleeding (ARIA-H).

Important Considerations and Risks

While promising, these plaque-dissolving therapies are not suitable for all individuals with Alzheimer's. They are currently approved for patients with mild cognitive impairment (MCI) or early-stage Alzheimer's disease who have confirmed amyloid plaque buildup. They are not intended for people with moderate or severe dementia. Key considerations include:

Amyloid-Related Imaging Abnormalities (ARIA): This is the most significant potential side effect, involving fluid buildup (ARIA-E) or small bleeds (ARIA-H) in the brain. While often asymptomatic, ARIA can, in rare cases, lead to serious or life-threatening complications. Regular brain MRIs are required to monitor for these changes during treatment. The risk of ARIA is higher for individuals who carry the APOE e4 gene, and genetic testing is recommended prior to beginning therapy.
Modest Efficacy: Though significant, the clinical benefit of these drugs is modest. Trials demonstrated a slowing of cognitive decline by approximately 27-35% over a period of 18 months, meaning they slow progression rather than halt or reverse the disease. The hope is that the benefit will increase with longer-term treatment.
Eligibility and Access: These are not universal cures. Patients must meet specific criteria, including a confirmed presence of amyloid plaques through PET scans or cerebrospinal fluid analysis, before being prescribed the medications.

Beyond Approved Drugs: The Future of Plaque-Clearing Research

Research into addressing brain plaque is a rapidly evolving field. Scientists are exploring multiple avenues to improve upon current therapies and develop new strategies for different stages of the disease.

Next-Generation Monoclonal Antibodies: Researchers are developing new antibodies with enhanced efficacy, improved safety profiles, and potentially more convenient administration methods, such as subcutaneous injections rather than IV infusions.
Targeting Other Proteins: Beyond amyloid, therapies are being developed to target abnormal tau proteins, which form neurofibrillary tangles inside brain cells and are also a key feature of Alzheimer's. Some research suggests that therapies combining anti-amyloid and anti-tau strategies may be needed for greater efficacy.
Drug Repurposing: In some studies, existing medications approved for other conditions, such as dasatinib (a leukemia drug) or bumetanide (a diuretic), have shown potential in modifying molecular pathways linked to Alzheimer's pathology.
Immune System Modulation: Other strategies focus on boosting the brain's own immune cleanup crews, known as microglia, to more effectively clear waste, including amyloid.
Dietary and Lifestyle Research: Laboratory studies have explored the potential of certain natural compounds, including green tea catechins, resveratrol, and vitamin D, to influence plaque formation, but these are not yet clinically validated treatments.

Conclusion

While a definitive cure for Alzheimer's remains elusive, recent advancements offer real hope. Monoclonal antibodies like lecanemab and donanemab represent the first truly disease-modifying therapies for early-stage Alzheimer's by providing a way to begin to dissolve plaque in the brain. They are not without risk and require careful management, but they offer a tangible way to slow the relentless progression of the disease. The ongoing research pipeline, exploring next-generation antibodies, alternative targets like tau, and novel approaches, suggests a future where Alzheimer's can be managed more effectively, giving patients and their families more precious time. Anyone considering these treatments should have a thorough discussion with their neurologist to weigh the benefits and risks based on their individual health profile.

For More Information

For more in-depth information and resources on Alzheimer's disease and its treatment, consult authoritative sources such as the National Institute on Aging (NIA).

Frequently Asked Questions

In Alzheimer's disease, the primary type of plaque that builds up in the brain is called beta-amyloid plaque. These sticky deposits accumulate outside of neurons, disrupting brain cell communication and function.

These medications are monoclonal antibodies that bind to specific forms of beta-amyloid protein. This process marks the plaques for clearance by the body's own immune system, gradually reducing their presence in the brain.

Eligibility is currently restricted to patients with mild cognitive impairment or early-stage Alzheimer's disease who have confirmed amyloid plaques in their brain. Patients with moderate to severe dementia are not candidates.

A primary risk is Amyloid-Related Imaging Abnormalities (ARIA), which can cause temporary brain swelling (ARIA-E) or micro-hemorrhages (ARIA-H). Regular MRI monitoring is necessary to manage this risk.

No, these therapies are not a cure. They are considered disease-modifying because they target the underlying pathology, but they only slow the rate of disease progression, rather than stopping or reversing it.

Lecanemab is typically administered via intravenous (IV) infusion every two weeks, while donanemab is given via IV infusion monthly. The frequency and duration of treatment vary depending on the medication.

Research is ongoing into other potential treatments, including therapies targeting tau protein tangles, repurposing existing drugs, and exploring natural compounds. However, aside from the approved monoclonal antibodies, these are still considered experimental.