A patient asked me this question last week, and it's the right question to ask. The AMBAR trial demonstrated that plasma exchange with albumin replacement slowed Alzheimer's progression by 52–71% across multiple outcome measures — effect sizes larger than lecanemab or donanemab, with essentially zero risk of brain swelling. Those results were independently replicated in a 2025 real-world study from Argentina. So why isn't this conversation happening in every neurology office in the country?
The answer isn't scientific. The evidence is there. The answer is structural — a convergence of industry economics, regulatory pathways, logistical barriers, and medical culture that makes it very difficult for a procedural intervention to compete with a pharmaceutical one, regardless of the data.
The Industry Dynamics
The monoclonal antibodies — lecanemab (Leqembi) and donanemab (Kisunla) — are backed by Biogen, Eisai, and Eli Lilly, companies that spent billions on development and clinical trials. They have dedicated neurology sales forces calling on every relevant prescriber, run direct-to-consumer advertising, fund continuing medical education, and support patient advocacy organizations. Their drugs are the story neurologists hear, repeatedly, from the moment they complete training.
AMBAR was sponsored by Grifols, a substantial company in the plasma protein therapeutics industry — but one without a meaningful neurology presence, without a sales force calling on neurologists, and promoting an off-label use of existing approved products rather than a patented new drug. The economic incentive structure heavily favors the monoclonal antibodies, independent of what the clinical data shows.
"The question isn't whether the evidence supports plasma exchange. It's why the medical establishment hasn't caught up to it yet."
The Regulatory Reality
Lecanemab and donanemab went through the traditional FDA drug approval pathway. That status matters enormously in clinical practice — physicians can prescribe with confidence, insurance coverage is often required, legal liability is clearer, and there's an established standard of care to point to.
Plasma exchange with albumin replacement is an off-label use of two products that are each individually FDA-approved. This creates real friction: some physicians are hesitant to use treatments off-label, insurance coverage is less predictable, reimbursement can be denied, and implementation requires more institutional coordination. None of this reflects on the evidence. It reflects on how medicine adopts new treatments.
The Logistics Problem
Prescribing lecanemab is straightforward — write a prescription, the patient goes to an infusion center every two weeks for a 30–60 minute infusion. Plasma exchange is more complex. It requires specialized apheresis equipment and trained staff, takes 2–3 hours per session, needs appropriate venous access, and requires coordination between neurology and apheresis services. Many medical centers don't have apheresis capabilities at all. It is simply easier, institutionally, to prescribe a drug than to implement a procedural intervention — regardless of which produces better outcomes.
Medical Culture and Paradigm
Neurologists are trained to think in terms of pharmaceutical interventions. Plasma exchange is a procedural, extracorporeal therapy more commonly associated with hematology and nephrology. There is natural resistance in any specialty to adopting treatment modalities that fall outside its typical scope of practice. A neurologist prescribing an antibody infusion feels familiar and professionally comfortable. Referring a patient for repeated plasma exchange sessions at an apheresis center feels foreign — even when the data favors the referral.
Study Size and Replication Lag
AMBAR enrolled 322 patients — well-designed and adequately powered for its endpoints, but smaller than the pivotal monoclonal antibody trials (1,795 for lecanemab, 1,182 for donanemab). Medicine generally wants to see large-scale replication before shifting widespread practice. The 2025 Argentina real-world study provides meaningful validation, but it enrolled 32 patients and used historical controls. A large multicenter randomized trial comparing plasma exchange directly to standard of care would likely be required to move the needle on prescribing behavior — and no pharmaceutical company has the financial incentive to fund it.
The Narrative Problem
Monoclonal antibodies have a simple, compelling story: remove the toxic plaques that cause Alzheimer's. One target, one mechanism, one drug. Plasma exchange has a more accurate but harder-to-communicate story: remove damaged proteins, reduce inflammation, restore antioxidant capacity, improve vascular function, and clear various harmful factors through mechanisms we don't yet fully understand. The simpler story wins in medical education, in physician conversations, and in patient-facing advertising — even when the more complex mechanism produces better results.
"No pharmaceutical company has a financial incentive to fund the large trial that would move plasma exchange into standard of care. That's not a conspiracy — it's just how drug development economics work."
What This Means for Patients
The practical implication is that you are unlikely to hear about plasma exchange from a neurologist who doesn't already know about it. This isn't malfeasance — it's the predictable result of how medical knowledge spreads. Physicians learn from journals, conferences, colleagues, and industry representatives. For plasma exchange in Alzheimer's disease, most of those channels are quiet.
This is why informed patients matter. If you or a family member has an Alzheimer's diagnosis — or cognitive symptoms that concern you — it is worth seeking out a physician with specific expertise in therapeutic apheresis and asking directly about whether plasma exchange is appropriate for your situation. The evidence exists. The access barrier is institutional, not scientific.
Conclusion
The AMBAR findings aren't obscure or contested. They were published in Alzheimer's & Dementia, independently replicated, and presented at major conferences. The amyloid-negative finding — showing that 30% of patients without hallmark Alzheimer's pathology benefited equally — has profound implications that the field has largely not grappled with. The treatment works. The question is whether patients can access it.
If you're asking why your doctor hasn't mentioned plasma exchange, the answer is probably not that they've evaluated it and rejected it. It's more likely that it simply hasn't entered their field of view. That gap is exactly what this journal exists to address.