The AMBAR Trial: What It Means for Alzheimer’s Patients and Families

If someone you love has been diagnosed with Alzheimer’s disease, you’ve probably been told there isn’t much that can be done. The FDA-approved drugs, lecanemab (Leqembi) and donanemab (Kisunla), slow decline modestly, by roughly 26–40% on clinical measures, and carry a 12–40% risk of brain swelling or bleeding serious enough to require MRI monitoring throughout treatment.

Most families don’t know there’s another option, one that showed stronger results in a rigorous clinical trial with essentially none of that risk.

Key Takeaways

• The AMBAR trial showed plasma exchange slowed Alzheimer’s progression by 52–71% across multiple measures, more than any FDA-approved drug
• Patients with mild Alzheimer’s actually improved on some functional measures over 14 months
• Only rare, asymptomatic ARIA — about 0.9% of treated patients in AMBAR — compared to 12–40% with monoclonal antibodies
• Results were independently confirmed by a 2025 real-world study in Argentina
• Earlier treatment appears to produce greater benefit

What the AMBAR Trial Showed

AMBAR (Alzheimer Management By Albumin Replacement) was a Phase 2b/3, multicenter, randomized, double-blind, placebo-controlled trial conducted across 41 sites in the United States and Spain. It randomized 347 patients with mild-to-moderate Alzheimer’s disease, of whom 322 received treatment, and followed them for 14 months.

The treatment was therapeutic plasma exchange (TPE), a procedure that removes aged, inflammatory plasma from the blood and replaces it with fresh albumin, the most abundant protein in human plasma. Patients in the placebo group underwent sham procedures designed to look and sound identical, so neither patients nor clinicians knew who was receiving real treatment.

Over 14 months, treated patients showed:

• 52% less decline in activities of daily living (managing medications, preparing meals, keeping appointments)
• 71% less decline on the CDR-Sum of Boxes, the broadest measure of overall function
• Near-complete stabilization on the clinician’s global assessment, while the placebo group continued to decline (p<0.0001)
• Only rare, asymptomatic ARIA (about 0.9% of treated patients), versus the brain swelling and bleeding that affects up to 40% of patients on newer monoclonal antibody drugs

Earlier Treatment Matters

One of the most important findings from AMBAR came from looking at how patients responded based on their stage of disease.

Patients with moderate Alzheimer’s showed the strongest and most consistent slowing of decline, roughly 61% on the two co-primary endpoints (with 50–71% across the secondary global measures).

But patients in the mild group showed something unexpected: on several global functional measures, they didn’t just decline more slowly. They actually improved from baseline over 14 months.

In a progressive neurodegenerative disease, improvement is not something clinicians expect to see. The fact that it appeared in the milder cases, where there’s presumably more functional capacity left to preserve and restore, carries a clear implication: the earlier treatment begins, the more benefit there is to capture.

AMBAR only enrolled patients with mild-to-moderate disease. It did not study advanced or severe Alzheimer’s. In our clinical experience, patients with severe or late-stage disease are unlikely to see meaningful benefit from plasma exchange. Once extensive neuronal loss has occurred, removing inflammatory and toxic factors from the blood can only do so much.

This is why we encourage families not to wait. If you or someone you love is in the early or moderate stages, the window for intervention is now.

Validated Beyond a Single Trial

A common and fair question about any clinical trial is whether the results hold up outside the original study.

In 2025, an independent research team in Argentina published a real-world study comparing 32 patients who received plasma exchange to 194 historical controls from the same memory clinic. Using different cognitive tests, a different protocol, and a completely independent patient population, they found 45–88% less decline across memory, language, and executive function. The effect sizes were remarkably consistent with AMBAR’s findings.

Two independent studies, in different countries, with different assessment tools, showing the same magnitude of benefit. That’s meaningful.

Why Global Apheresis

Understanding the AMBAR data is one thing. Accessing the treatment is another.

Most neurologists haven’t heard of the AMBAR trial. Plasma exchange isn’t part of the standard neurology toolkit. It requires specialized apheresis equipment, trained nursing staff, and physicians with deep experience in the procedure. The vast majority of medical centers don’t offer it for Alzheimer’s patients.

Global Apheresis exists specifically to bridge that gap.

Our founder, Dr. Dobri Kiprov, is one of the physicians who established therapeutic plasma exchange as a clinical discipline. He has overseen more than 15,000 TPE procedures over four decades of practice and has authored over 100 peer-reviewed publications in the field.

He completed his fellowship in Clinical Immunology and Immunopathology at Massachusetts General Hospital and Harvard Medical School, and is a founding member of the American Society for Apheresis.

This isn’t a practice that read about AMBAR and decided to offer plasma exchange. This is a practice built on the expertise that made trials like AMBAR possible.

What Treatment Looks Like

For families picturing something clinical and intimidating, the reality is more straightforward than you might expect.

TPE is performed on an outpatient basis in our Mill Valley clinic. Each session takes approximately two to three hours. Blood is drawn through a vein in the arm, the apheresis machine separates and removes the plasma, and your blood cells are returned along with fresh albumin replacement.

Our nurses monitor you throughout, and most patients describe the experience as uneventful, similar to sitting for a long blood donation. There is no surgery, no anesthesia, and no hospital stay.

For Alzheimer’s patients, a typical course begins with an intensive series of six procedures. These don’t need to be done on a rigid weekly schedule. Sessions can be spread across six weeks, condensed into two or three weeks, or arranged in whatever pattern fits the patient’s life and travel plans.

In our clinical experience, flexibility in the intensive-phase scheduling has not altered outcomes, so we work with each family to find a rhythm that’s practical. Following the intensive series, a maintenance protocol of one procedure per month is recommended, consistent with the protocol used in the AMBAR trial.

Is This Right for Your Family?

TPE for Alzheimer’s disease is classified as an ASFA Category III indication, meaning the evidence is promising and growing, but it has not yet become a mainstream first-line recommendation. We believe the data speaks clearly, but we also believe families deserve full transparency about where the science stands.

The clinical evidence demonstrates that plasma exchange slows Alzheimer’s progression more than any currently available drug, with a dramatically better safety profile. The results have been independently replicated. And our practice has more experience performing this procedure than virtually any clinic in the country.

If someone you love has been diagnosed with mild or moderate Alzheimer’s disease and you want to understand whether therapeutic plasma exchange is appropriate for their situation, we’d welcome that conversation.

A discovery call with one of our physicians is complimentary and carries no obligation. Most consultations are conducted via telehealth, so you don’t need to be local to start.

Dr. Allen P. Green is the Associate Medical Director of Global Apheresis in Mill Valley, California. He is Board-Certified in Clinical Pathology and has personally performed over 500 TPE procedures. For a detailed analysis of the AMBAR trial data, including the biomarker findings, the Argentina validation study, and the comparison to FDA-approved drugs, see The AMBAR Series on Dr. Green’s research journal.

References

• Boada M, Lopez OL, Olazaran J, et al. “A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer’s disease: Primary results of the AMBAR Study.” Alzheimer’s & Dementia. 2020;16(10):1412–1425.
• Taragano F, Seinhart D, Epstein P, et al. “A real-world study on the safety and efficacy of therapeutic plasma exchange in patients with Alzheimer’s disease.” Journal of Alzheimer’s Disease. 2025;108(1):129–141.