The AMBAR hypothesis


The AMBAR hypothesis

In the brains of Alzheimer's patients, neuronal damage appears to be related to the build-up of two proteins: beta-amyloid and tau. Beta-amyloid circulates in plasma bound to its most abundant protein, albumin. It is also present in cerebrospinal fluid (CSF), in dynamic equilibrium with the beta-amyloid in plasma.

AMBAR is an innovative treatment proposal aimed at slowing the progression of Alzheimer's disease through periodic plasma exchange. It is based on a dual-action mechanism: Plasma containing beta-amyloid bound to albumin is extracted through plasmapheresis, a technique developed by Grifols in 1951. The extracted plasma is then replaced with albumin, which is a widely used protein that has binding, antioxidant and immunomodulatory properties.

The treatment is based on the hypothesis that periodic plasma exchange might disrupt the CSF-plasma dynamic equilibrium and drawing beta-amyloid from the brain into the plasma. Some beta-amyloid would be removed through the initial extraction. Meanwhile, the new albumin could bind to and capture more beta-amyloid and other harmful factors.

In this way, the build-up of beta-amyloid could be reduced before it can cause neuronal damage, thus limiting the impact of Alzheimer's disease on cognition.

The video explains the main hypothesis of the AMBAR study, which is based on a dual-action mechanism: plasmapheresis and albumin replacement.

Plasma is the liquid portion of the blood.

About 90% is composed of water, while the remaining 10% contains thousands of essential proteins. The most abundant protein is Albumin, which has strong binding, antioxidant, and immunomodulatory properties.


Plasmapheresis is a procedure developed by Grifols in the 1950s.

It is an established and safe technique that allows separating plasma from other blood components (red blood cells, platelets and other cells), which are injected back into the donor during the donation process. It is currently the most widely used technique for collecting plasma from donors for therapeutic purposes.

What is plasma exchange?

Patients participating in the AMBAR clinical trial were treated with periodic plasma exchange: a safe, well-known therapy based on the plasmapheresis technique.

In Therapeutic Plasma Exchange (TPE), blood is taken from the patient's arm through a tube connected to the exchange machine. In this machine, the blood is separated into its various parts: plasma and cellular components. The plasma is replaced with a fluid – albumin in most cases– which is added to the remaining blood cells. This new solution is injected back to the patient.

TPE is not painful so it does not require anesthesia. The therapy is usually given in hospitals or at an outpatient center and is currently used to treat a range of blood, neurological and autoimmune diseases.