Immunotherapy has emerged as the most significant advance in Alzheimer’s treatment in decades, and for the first time, it offers patients something the field has long lacked: a therapy that directly targets and slows the underlying disease process rather than just managing symptoms. Two drugs — lecanemab (Leqembi) and donanemab (Kisunla) — have now received full FDA approval for early-stage Alzheimer’s. They work by recruiting the immune system to clear toxic amyloid beta proteins from the brain, slowing cognitive decline in patients with confirmed amyloid plaques. For a person in the early stages of the disease — still living independently, managing daily tasks, but noticing memory slips — these drugs represent a real, if modest, chance to extend that window of functional independence.
The role immunotherapy plays is not a cure. That point deserves emphasis upfront. These therapies slow progression; they do not reverse damage already done or restore lost memory. But in a disease that has defeated every treatment attempt for over two decades, slowing cognitive decline by 27 to 35 percent is a meaningful clinical result. This article covers how these approved drugs work, who qualifies for them, what the serious risks are, and what the next wave of immunotherapy research — including CAR-T cell therapy tested in early 2026 — looks like for patients and families watching closely.
Table of Contents
- How Does Immunotherapy Work Against Alzheimer’s Disease?
- Who Qualifies for Immunotherapy — and Who Does Not?
- What Are the Risks of Anti-Amyloid Immunotherapy?
- How Are These Drugs Administered, and What Changed in 2025?
- What Does the Research Pipeline Look Like Beyond Approved Drugs?
- The Role of Personalized Medicine in Alzheimer’s Immunotherapy
- Where Is Alzheimer’s Immunotherapy Headed?
- Conclusion
- Frequently Asked Questions
How Does Immunotherapy Work Against Alzheimer’s Disease?
Alzheimer’s disease is characterized by the accumulation of two abnormal protein deposits in the brain: amyloid beta plaques and tau tangles. For years, the dominant hypothesis held that amyloid buildup was a primary driver of neuronal damage. Immunotherapy approaches in Alzheimer’s take direct aim at this target by using engineered antibodies — proteins designed to bind to amyloid beta and flag it for removal by the immune system. This is called passive immunotherapy, because the patient receives pre-made antibodies rather than generating their own immune response. Lecanemab, for example, specifically targets amyloid beta protofibrils — the soluble, toxic intermediate forms of amyloid that are thought to be especially damaging before they fully aggregate into plaques. When administered intravenously, lecanemab binds to these protofibrils and plaques and prompts the brain’s immune cells to clear them.
The clinical trial data showed a 27% slowing of cognitive decline over 18 months compared to placebo. Donanemab targets a modified form of amyloid found specifically in established plaques and showed approximately 35% lower risk of disease progression in late-stage trials. The comparison between these two drugs is meaningful for patients trying to understand their options. Lecanemab clears protofibrils and plaques; donanemab focuses on the more mature plaque deposits. Both require confirmed amyloid burden — through PET scan or cerebrospinal fluid testing, or now through newer blood tests — before treatment can begin. Neither drug has been shown to benefit patients in moderate or late-stage Alzheimer’s, where significant neuronal loss has already occurred.
Who Qualifies for Immunotherapy — and Who Does Not?
Both lecanemab and donanemab are approved only for early symptomatic Alzheimer’s — specifically, patients with mild cognitive impairment (MCI) or mild dementia who have confirmed amyloid pathology. This is a critical limitation. The majority of people with Alzheimer’s who are currently living with the disease are in moderate or advanced stages, which means they are not eligible candidates for these treatments. If a loved one has already progressed beyond the mild stage, these immunotherapies are not currently an option. Eligibility also depends on confirming amyloid presence in the brain, which historically required either a PET scan (expensive and not always covered by insurance) or a lumbar puncture for cerebrospinal fluid analysis.
A significant development in May 2025 changed this landscape: the FDA approved the Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio blood test, which can detect Alzheimer’s pathology through a standard blood draw. This approval makes screening for amyloid burden considerably more accessible and is expected to expand the pool of patients who can be identified as eligible for immunotherapy. However, there are additional contraindications that must be weighed carefully. Patients carrying two copies of the APOE4 gene — a genetic variant associated with higher Alzheimer’s risk — face elevated risk of serious side effects from anti-amyloid drugs. Anyone considering treatment should undergo genetic testing and have a detailed conversation with their neurologist about individual risk factors before starting either therapy.
What Are the Risks of Anti-Amyloid Immunotherapy?
The most significant safety concern with both lecanemab and donanemab is a condition called ARIA — Amyloid-Related Imaging Abnormalities. This refers to brain swelling (ARIA-E) or microbleeds (ARIA-H) that can occur as the immune system responds to the clearing of amyloid from blood vessel walls. In clinical trials, ARIA was common: it appeared in roughly 21% of lecanemab-treated patients and in higher proportions among APOE4 carriers. Most cases were mild and detectable only on MRI without causing noticeable symptoms. But a small number of patients experienced serious neurological events, and three deaths during trials were potentially linked to ARIA. This is not a theoretical risk to minimize.
The FDA requires regular MRI monitoring during treatment precisely because ARIA can escalate without obvious symptoms. If a patient develops significant ARIA, treatment is paused or discontinued. For patients on blood thinners or with other vascular risk factors, the risk calculus becomes more complex and requires careful clinical judgment. The practical implication for patients and families is that starting one of these therapies is not like beginning a standard medication. It requires access to an infusion center, regular neuroimaging, and a medical team experienced with monitoring for ARIA. Not all neurology practices are equipped to manage this, and access remains uneven across geographic regions.
How Are These Drugs Administered, and What Changed in 2025?
When lecanemab first received full FDA approval in July 2023, it required intravenous infusions every two weeks — a significant logistical burden for patients and caregivers. In January 2025, the FDA approved a maintenance dosing schedule that reduces infusions to once every four weeks after an initial 18-month treatment period. This change addresses one of the most common practical complaints from patients and families managing the demands of regular clinic visits. Then, in August 2025, the FDA approved an entirely new formulation: Leqembi IQLIK, a subcutaneous (under-skin) injection that can be self-administered once weekly.
This is a meaningful shift. Moving from an IV infusion at an infusion center to a self-administered injection at home removes a substantial logistical barrier for patients in rural areas, those without reliable transportation, and caregivers managing complex care schedules. The tradeoff is that injections require patient or caregiver training and consistent self-discipline in administration. Donanemab’s administration profile is different in an important way: clinical trial data showed that patients who cleared their amyloid plaques completely were able to stop treatment entirely, with some maintaining their benefit even after discontinuation. This “treat to clearance” model is clinically distinct from lecanemab’s ongoing maintenance approach and may factor into prescribing decisions based on a patient’s specific amyloid burden and treatment response.
What Does the Research Pipeline Look Like Beyond Approved Drugs?
The scope of Alzheimer’s drug development has grown dramatically. As of 2025, there are 138 drugs being evaluated across 182 clinical trials, targeting 15 different disease mechanisms — including amyloid, tau, neuroinflammation, and brain metabolism. The NIH is funding 495 clinical trials for Alzheimer’s and related dementias, with more than 225 testing pharmacological interventions. This is not a field standing still. One of the most closely watched emerging approaches is CAR-T cell therapy. In February 2026, researchers at Washington University and the Weizmann Institute published findings showing that engineered CAR-T immune cells — similar to those used in some blood cancer treatments — could be programmed to target amyloid beta plaques in the brain.
In mouse models, these cells produced greater plaque reduction than control T cells and also reduced harmful activation of microglia and astrocytes, the brain’s immune cells that can cause additional damage when chronically activated. This is early-stage research, and the leap from mouse models to human trials is significant, but the direction is notable. The critical warning here is that a pipeline of 138 drugs does not mean 138 near-term treatments. The overwhelming majority of Alzheimer’s drug candidates have failed in clinical trials over the past two decades. What the current pipeline reflects is a broader, more diversified approach — targeting tau alongside amyloid, addressing neuroinflammation, and exploring metabolic pathways — rather than the single-target focus that defined earlier efforts. Progress is real, but the distance between promising preclinical results and an approved therapy remains long.
The Role of Personalized Medicine in Alzheimer’s Immunotherapy
A 2025 study published in Frontiers in Medicine explored the potential of integrating genetic and immune profiles to individualize Alzheimer’s immunotherapy — an approach that recognizes that not all patients respond identically to the same treatment. APOE genotype, existing immune function, amyloid burden, and the presence of tau pathology all likely influence how a given patient will respond. The aspiration is to move toward treatment protocols tailored to a patient’s specific biological profile rather than applying a one-size-fits-all antibody therapy.
This is particularly relevant given the complexity of ARIA risk stratification. Identifying in advance which patients are likely to develop serious ARIA — based on genetic markers, imaging characteristics, and immune profiles — could allow for more precise patient selection and monitoring protocols. For families navigating treatment decisions, understanding that personalized approaches are being developed may reframe the conversation with neurologists about whether to pursue current immunotherapy now or wait for more refined options.
Where Is Alzheimer’s Immunotherapy Headed?
Research published in February 2026 identified brain mechanisms — described informally as “switches” — that can be activated to clear Alzheimer’s plaques, potentially opening new immunotherapy targets independent of the antibody approach that has defined the field to date. This suggests that the biological toolkit for targeting amyloid may expand significantly beyond monoclonal antibodies to include approaches that amplify the brain’s own clearance systems.
The trajectory of the field points toward combination therapies — much like how cancer treatment evolved from single-agent chemotherapy to multi-drug regimens — that address amyloid, tau, and neuroinflammation simultaneously. The identification of reliable blood-based biomarkers like the pTau217 test approved in 2025 means that screening, diagnosis, and monitoring will increasingly happen through accessible blood draws rather than expensive PET scans. That shift alone could dramatically expand the number of patients identified early enough to benefit from current and future immunotherapies.
Conclusion
Immunotherapy has changed the fundamental reality of Alzheimer’s treatment. For the first time, patients in the early stages of the disease — those who can still be identified through amyloid testing before significant neuronal loss has occurred — have access to FDA-approved drugs that directly slow the underlying biology driving their decline. Lecanemab and donanemab are imperfect treatments: they carry real risks, require careful monitoring, and help only a subset of patients.
But they represent a genuine scientific achievement in a disease that had produced no meaningful therapeutic advance for over two decades. For families and patients, the most important practical takeaways are these: early identification matters enormously, because these therapies only work at the beginning of the disease course; new blood tests have made amyloid screening more accessible; and the risk-benefit calculation is individual and nuanced, particularly for APOE4 carriers. The research pipeline — from CAR-T cell therapy to personalized immunotherapy protocols — is broader and more sophisticated than at any previous point. The goal of not just slowing but halting Alzheimer’s progression remains unmet, but the field is closer to it than it has ever been.
Frequently Asked Questions
Are lecanemab and donanemab covered by Medicare?
Medicare covers lecanemab (Leqembi) for eligible patients who meet the criteria established by CMS, including confirmed diagnosis of early Alzheimer’s and amyloid confirmation. Coverage requires enrollment in a qualifying registry or clinical study in some contexts. Coverage policies for donanemab (Kisunla) are still being finalized in many plans. Patients should contact their specific plan and work with their neurologist’s billing team to determine coverage before beginning treatment.
Can someone with moderate or late-stage Alzheimer’s receive immunotherapy?
Currently, no. Both approved anti-amyloid drugs — lecanemab and donanemab — are approved only for mild cognitive impairment or mild dementia with confirmed amyloid pathology. Patients in moderate or late stages are not eligible for these therapies, and clinical trials have not shown benefit in those populations.
What is ARIA, and how serious is it?
ARIA stands for Amyloid-Related Imaging Abnormalities — brain swelling or microbleeds that can occur as amyloid is cleared from blood vessels. Most cases are mild and detected only on MRI. Serious cases involving neurological symptoms are less common but do occur. Patients on blood thinners or with two copies of the APOE4 gene are at higher risk. Regular MRI monitoring during treatment is required to catch ARIA early.
How does the new blood test change access to immunotherapy?
The FDA-approved Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio blood test, approved in May 2025, allows physicians to detect Alzheimer’s amyloid pathology through a standard blood draw rather than requiring a PET scan or lumbar puncture. This significantly lowers the cost and logistical barrier to confirming eligibility for anti-amyloid therapy.
Is CAR-T cell therapy for Alzheimer’s available to patients now?
No. CAR-T cell therapy for Alzheimer’s is still in early preclinical research — the published findings from February 2026 involved mouse models. Human clinical trials have not yet begun. It remains a promising but distant prospect.
Does donanemab require ongoing treatment indefinitely?
Not necessarily. Clinical trial data for donanemab showed that some patients who fully cleared their amyloid plaques were able to discontinue treatment and maintain their benefit. This “treat to clearance” approach distinguishes donanemab from lecanemab, which uses an ongoing maintenance dosing schedule. Whether a specific patient can stop treatment depends on imaging confirmation of amyloid clearance.
