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 equilibrium with the beta-amyloid in plasma.

AMBAR is an innovative clinical trial aimed at slowing down the progression of Alzheimer's disease through periodic therapeutic plasma exchange.

AMBAR targets a multimodal approach to the management of the disease based on the hypothesis that most of the amyloid-beta protein is bound to albumin and circulates in plasma. Extracting this plasma may flush amyloid-beta peptide from the brain into the plasma, thus potentially limiting the disease's impact on the patient's cognitive functions. Additionally, albumin has binding capacity and antioxidant properties, and both albumin and immunoglobulin display immunomodulatory and anti-inflammatory properties.

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

This video explains the main hypothesis of the AMBAR study, based on a multimodal approach that includes periodic therapeutic plasma exchange.

Plasma is the liquid portion of blood.

About 90% is water, while the remaining 10% contains thousands of essential proteins. The most abundant protein is albumin, which has strong binding, antioxidant and immunomodulatory properties. Immunoglobulins, also known as antibodies, account for 15% of the plasma-protein content.


Plasmapheresis is a procedure developed by Grifols in 1951.

It is an established and safe technique that separates plasma from other blood components (red blood cells, platelets and other cells), which are injected back into the plasma 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, a plasma protein–which is added to the remaining blood cells. This new solution is injected back to the patient.

TPE 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.