Alzheimer’s disease: a study sponsored by AP-HP identifies early protective role of the immune system

For the first time in humans, an imaging study shows early and protective role of immune cells in the brain, called "microglia" in Alzheimer's disease. The teams of the CHU Sainte-Anne, the CEA, Saint-Antoine research center, the Institute for Brain and Spinal Cord Disorders (Inserm / CNRS / UPMC) and Roche researchers have identified a benefit of inflammatory mechanisms the early or preclinical stages, in a group of 96 subjects. This discovery opens up new therapeutic approaches to slow or even prevent the progression of Alzheimer's disease. This work, from the IMABio3 study * sponsored by AP-HP, are the subject of a publication on 16 March in the journal Brain.

Alzheimer disease is characterized by the abnormal accumulation in the brains of tau and amyloid proteins, forming the amyloid plaques. The appearance of these plates causes immune cell activation and inflammation of the brain, the main actors are the microglial cells. However, the exact role of these cells is still under debate: inflammation allows it to protect the brain against the disease or is it aggravates the course of the disease?

To answer this question, the research team analyzed, involving 96 subjects, microglial activity through the use of a new generation of tracer in Positron Emission Tomography (PET) in the Service Hospitalier Frédéric Joliot (Orsay , 91). In parallel, the amyloid plaques were quantified by brain imaging in the same patients.

The results show not only that the activation of microglia is associated with the presence of amyloid plaques, but also it is particularly important that the disease is at an early stage. To measure its impact on the evolution of symptoms, patients were followed for two years. Those whose microglial activity was initially high remained broadly stable clinically, while patients with low initial microglial activity evolved unfavorably to a decline of autonomy. This suggests a protective role of microglial inflammatory reaction on the evolution of the disease.

In addition, this mechanism seems to appear at the preclinical stage, since the activation of microglial cells was observed in asymptomatic subjects at risk of Alzheimer's disease (ie, the presence of amyloid plaques was observed but no health effect). However, at some stage, when the disease progresses, the inflammation could "pack" then becomes deleterious.

This study, the first of this magnitude ever conducted in men with this innovative brain imaging technique, shows the beneficial and protective role of the immune system in the early stages of Alzheimer's disease. It stresses the importance of diagnose the disease earlier and opens new therapeutic perspectives for slow or prevent its development.