Anti-amyloid therapy represents the first class of treatments that targets the underlying biology of Alzheimer’s disease rather than just managing its symptoms. The role of these drugs is to clear amyloid-beta plaques from the brain — the protein deposits long considered central to Alzheimer’s pathology — and in doing so, slow the rate at which patients lose cognitive function. Two drugs are now FDA-approved for this purpose: lecanemab (Leqembi), made by Eisai and Biogen, and donanemab (Kisunla), made by Eli Lilly. Clinical trials show both slow cognitive decline by approximately 25 to 30 percent over 18 months in patients with early-stage Alzheimer’s disease. That figure deserves careful interpretation.
A 25 to 30 percent slowing of decline does not mean reversal. It does not restore memory. It means that, compared to patients receiving a placebo, those on these drugs declined somewhat more slowly over a year and a half. For someone in the early stages of the disease — still independent, still recognizing family — that difference can matter. But the drugs do not work for everyone equally, they carry meaningful risks, and they are only effective when started early. This article covers how these therapies work, who benefits most, the significant safety concerns around brain swelling and bleeding, the limitations researchers continue to debate, and what the emerging pipeline looks like heading into 2026.
Table of Contents
- How Does Anti-Amyloid Therapy Work in Alzheimer’s Disease?
- Which Patients Are Eligible and Who Benefits Most from Anti-Amyloid Treatment?
- What Are the Safety Risks — Understanding ARIA
- Lecanemab vs. Donanemab — Comparing the Two Approved Therapies
- The Ongoing Debate About Clinical Meaningfulness
- Real-World Performance and What Post-Market Data Is Showing
- What the Pipeline Looks Like for 2026 and Beyond
- Conclusion
- Frequently Asked Questions
How Does Anti-Amyloid Therapy Work in Alzheimer’s Disease?
Anti-amyloid therapies are monoclonal antibodies — engineered proteins designed to identify and bind to amyloid-beta, the sticky protein fragment that accumulates into plaques between neurons in the Alzheimer’s brain. Once bound, the antibody flags the amyloid for removal by the immune system, gradually clearing deposits that have built up over years or even decades. This is a departure from every previous Alzheimer’s treatment, which worked downstream — alleviating neurotransmitter imbalances, for example — without touching the plaques themselves. The amyloid hypothesis, which holds that amyloid-beta accumulation is a primary driver of Alzheimer’s neurodegeneration, has guided drug development for over two decades. Anti-amyloid antibodies are the first to validate that hypothesis in a meaningful clinical sense.
Earlier attempts, including aducanumab (which received controversial accelerated FDA approval in 2021 before being withdrawn from the market), cleared amyloid on PET scans but failed to convincingly demonstrate cognitive benefit. Lecanemab and donanemab succeeded where others did not, partly because trials enrolled patients specifically at the earliest stages of disease, when plaque burden is high but neuronal damage is not yet catastrophic. A useful comparison: think of amyloid plaques as a slow structural fire in the brain. Anti-amyloid antibodies act as suppressants that reduce the fire’s spread — they do not rebuild what has already burned. That framing helps explain both the promise and the ceiling of these therapies. The earlier the intervention, the less damage has accumulated, and the more there is to preserve.
Which Patients Are Eligible and Who Benefits Most from Anti-Amyloid Treatment?
Both lecanemab and donanemab are indicated only for early-stage Alzheimer’s disease — specifically, patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s. Eligibility also requires confirmed amyloid pathology, typically established through amyloid PET imaging or cerebrospinal fluid biomarkers. The drugs have not demonstrated benefit in moderate or late-stage disease. For patients already experiencing significant functional decline, these treatments are not an option. Within the eligible population, outcomes are not uniform.
Clinical trial data shows that the greatest cognitive slowing was observed in White and Caucasian patients and in individuals who do not carry the APOE4 gene variant. APOE4 is the strongest genetic risk factor for late-onset Alzheimer’s, carried by roughly 25 percent of the general population and a higher proportion of Alzheimer’s patients. APOE4 carriers not only show less cognitive benefit from these drugs in some analyses — they also face substantially higher risks of serious side effects. This means the risk-benefit calculation looks very different for an APOE4 carrier than for a non-carrier with the same clinical presentation. The practical implication is that APOE4 genetic testing has moved from a research tool to a clinical consideration in the context of these treatments. Patients and families should understand that eligibility for anti-amyloid therapy is not simply a matter of diagnosis and timing — genetic profile, demographic factors, and individual health history all shape whether the expected benefits outweigh the expected risks for any given person.
What Are the Safety Risks — Understanding ARIA
The most significant safety concern associated with anti-amyloid therapy is a condition called ARIA, or Amyloid-Related Imaging Abnormalities. ARIA refers to brain swelling (ARIA-E, for edema or effusion) and small bleeds or microhemorrhages (ARIA-H) that can occur as the immune system responds to amyloid clearance. In more serious cases, a related finding called superficial siderosis — iron deposits on the brain’s surface from repeated small bleeds — has also been observed. Patients on lecanemab or donanemab have a 4.35 times higher relative risk of ARIA compared to patients receiving placebo. The majority of ARIA cases are asymptomatic and detected only on the regular MRI monitoring that the treatment protocol requires.
However, some patients experience headaches, confusion, dizziness, vision changes, or in rare cases, more severe neurological symptoms. Deaths have been reported in connection with ARIA, though these cases are uncommon and often involve patients who were also on blood-thinning medications. APOE4 carriers are at substantially elevated risk for ARIA, which is why genetic counseling before starting treatment is not optional — it is a clinical necessity. The treatment protocols for both drugs include mandatory MRI monitoring at regular intervals precisely because ARIA can develop without obvious symptoms and requires prompt medical evaluation when it does. Patients and caregivers considering anti-amyloid therapy should understand that this is not a simple infusion regimen; it involves ongoing imaging surveillance and the possibility of pausing or stopping treatment if ARIA develops.
Lecanemab vs. Donanemab — Comparing the Two Approved Therapies
Both lecanemab and donanemab are FDA-approved monoclonal antibodies targeting amyloid-beta, but they differ in their targets, dosing schedules, and some clinical characteristics. Lecanemab targets soluble amyloid-beta protofibrils — an earlier, more mobile form of the protein — while donanemab targets pyroglutamate-modified amyloid-beta embedded in mature plaques. Whether this mechanistic difference translates into meaningfully different patient outcomes in practice is still being studied. Donanemab has the notable feature of being given for a finite treatment period. In clinical trials, patients who achieved sufficient amyloid clearance on PET imaging were able to stop treatment — an important practical distinction, since indefinite infusion regimens are burdensome and costly.
Lecanemab, by contrast, is designed as ongoing maintenance therapy. In August 2025, Eisai received FDA approval for a subcutaneous formulation of lecanemab — meaning patients can self-administer maintenance doses at home by injection rather than traveling to an infusion center. That development meaningfully addresses one of the most common practical barriers to treatment adherence. On efficacy, meta-analyses confirm that both drugs outperform placebo on multiple validated cognitive scales, including ADCOMS, CDR-SB, and ADAS-Cog 14. Neither drug has been tested head-to-head in a direct comparison trial, so statements about one being superior to the other are not supported by the current evidence. The choice between them, where both are accessible, currently comes down to dosing convenience, individual patient profile, physician experience, and insurance coverage — not a clear efficacy advantage.
The Ongoing Debate About Clinical Meaningfulness
The FDA approval of lecanemab and donanemab has not ended scientific debate — it has intensified it. Critics point to a core concern: while both drugs achieve measurable amyloid clearance on PET scans and produce statistically significant reductions in cognitive decline rates, the absolute magnitude of benefit at the individual patient level is modest. Nearly four dozen clinical trials conducted since 2018 collectively indicate only marginal reduction in cognitive decline rate at the population level. The relationship between amyloid-PET clearance and meaningful clinical improvement has not been established at the individual patient level. This distinction matters. A drug can consistently clear amyloid in trial participants and still leave any given patient unable to point to a meaningful difference in their daily life.
The composite cognitive scores used in trials — ADCOMS, CDR-SB — measure change with precision, but a point or two on a rating scale does not always correspond to something a patient or caregiver notices. Researchers and clinicians are actively working to define what a clinically meaningful response looks like for an individual, rather than a statistical average across thousands of trial participants. Cost is another serious limitation. These are among the most expensive drugs in modern medicine, and coverage decisions by insurers and Medicare have created an uneven landscape of access. High cost has been widely noted as a significant barrier to equitable treatment in 2025. A patient who meets all clinical criteria — early-stage disease, confirmed amyloid, acceptable genetic risk profile — may still be unable to access treatment because of where they live, what insurance they carry, or the availability of specialized infusion centers and PET imaging in their region.
Real-World Performance and What Post-Market Data Is Showing
One concern with translating clinical trial results into clinical practice is that trials enroll carefully selected patients who may not reflect the full diversity of people seeking treatment. Real-world data collected since lecanemab’s approval has been watched closely by the research community for signs that outcomes might diverge from trial results — for better or worse.
Early real-world reports suggest that treatment outcomes in clinical settings are comparable to those observed in trials, which is reassuring. However, real-world populations include patients who might not have qualified for trials due to medical complexity, concurrent medications (particularly anticoagulants that elevate ARIA risk), or the inability to complete required MRI monitoring. The expanded use of these drugs in practice has reinforced that careful patient selection, genetic counseling, and consistent imaging surveillance are not bureaucratic formalities — they are the scaffolding that makes the therapy’s risk-benefit profile manageable.
What the Pipeline Looks Like for 2026 and Beyond
The current generation of FDA-approved anti-amyloid therapies is likely not the final chapter. Trontinemab, a next-generation anti-amyloid antibody engineered with a mechanism designed to improve brain penetration and potentially reduce ARIA risk, entered Phase III trials as of 2025. Small-molecule approaches targeting amyloid-beta oligomers — the most toxic, soluble forms of the protein thought to damage neurons most acutely — are also in development, with the goal of enabling oral rather than injectable treatment and potentially reaching patients earlier in the disease process.
Perhaps the most consequential development came in December 2025, when new research from UCSF suggested that anti-amyloid drugs could potentially prevent Alzheimer’s dementia before memory loss begins — in pre-symptomatic individuals who carry biomarker evidence of amyloid accumulation but have not yet developed clinical symptoms. If that hypothesis is borne out in prevention trials, the target population for anti-amyloid therapy could expand dramatically, and the entire model of when to intervene would shift from treating early disease to preventing its clinical onset altogether. That remains a research horizon, not a current clinical reality — but it represents the most significant possible evolution of this treatment class.
Conclusion
Anti-amyloid therapy has changed the landscape of Alzheimer’s treatment by offering, for the first time, drugs that address the disease’s underlying pathology rather than only its symptoms. Lecanemab and donanemab both slow cognitive decline by roughly 25 to 30 percent in early-stage patients, are supported by robust clinical trial data, and are now FDA-approved with expanding access through formulations like subcutaneous lecanemab. The question is no longer whether these drugs work in a clinical trial sense — it is who they work for, how much, and at what risk. The ARIA safety profile, the APOE4 risk differential, the limitations of cost and access, and the honest uncertainty about individual-level clinical benefit all remain central to any serious conversation about these treatments.
For patients and families navigating an Alzheimer’s diagnosis, the most practical takeaway is this: these treatments are only an option in the early stages of the disease, and the window for eligibility is narrow. Cognitive symptoms that emerge gradually are often not evaluated for amyloid confirmation until the disease has already progressed past the point where anti-amyloid therapy is indicated. Early evaluation — ideally through a memory specialist or dementia-focused clinic before symptoms are severe — is what creates the possibility of access. As the pipeline develops and prevention trials advance, the calculus may shift. For now, timing and early clinical engagement are the determining factors in whether anti-amyloid therapy is a realistic option.
Frequently Asked Questions
Are lecanemab and donanemab the same drug?
No. They are both monoclonal antibodies that target amyloid-beta, but they work slightly differently. Lecanemab (Leqembi) targets soluble amyloid protofibrils, while donanemab (Kisunla) targets a specific modified form of amyloid in mature plaques. They have different dosing schedules and some differences in their clinical profiles.
Can someone with moderate or late-stage Alzheimer’s use these drugs?
No. Both lecanemab and donanemab are approved only for early-stage Alzheimer’s — specifically mild cognitive impairment or mild dementia with confirmed amyloid pathology. There is no demonstrated benefit in moderate or late-stage disease, and trials have not been conducted for those populations.
What does ARIA feel like, and how serious is it?
Most cases of ARIA produce no noticeable symptoms and are detected only through the mandatory MRI monitoring that the treatment protocol requires. When symptoms do occur, they can include headache, confusion, dizziness, or vision changes. Severe cases are uncommon but can occur, particularly in patients on blood thinners or those with the APOE4 gene variant.
Does having the APOE4 gene mean you cannot take these drugs?
Not necessarily, but APOE4 carriers face higher ARIA risk and, in some analyses, show less cognitive benefit. Genetic counseling is strongly recommended before starting treatment. The risk-benefit assessment is more complex for APOE4 carriers, and some specialists may recommend against treatment depending on the individual’s overall clinical picture.
How is amyloid confirmed before starting treatment?
Amyloid pathology can be confirmed through amyloid PET imaging, which shows plaque deposits in the brain, or through cerebrospinal fluid biomarkers. Both methods are used in clinical practice, though availability and cost vary significantly by location.
Is lecanemab now available as a home injection?
Yes. As of August 2025, the FDA approved a subcutaneous (under the skin) formulation of lecanemab for maintenance dosing, allowing eligible patients to self-administer doses at home rather than attending infusion centers. This applies to the maintenance phase of treatment, not the initial loading doses.
