Research Published March 18 2016
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For the first time in humans, an imaging study shows an early and protective role of the immune cells of the brain, called ” microglial ” cells, in Alzheimer’s disease. Teams from the Sainte-Anne Hospital Center, from the CEA, from the Saint-Antoine research center, from the Brain and Spine Institute (Inserm / CNRS / UPMC) and researchers from Roche have identified a benefit of inflammatory mechanisms in early, or even pre-clinical stages, in a group of 96 subjects. This discovery paves the way for new therapeutic leads to slow, or even prevent, the progression of Alzheimer’s disease. This work, based on IMABio3* study, promoted by AP-HP, is the subject of a publication on March 15, 2016 in Brain magazine.

Alzheimer’s disease is characterized by abnormal accumulation in the brain of tau and amyloid protein, forming amyloid plaques. Formation of these plaques leads to immune and inflammatory brain cells activation, which main actors are microglial cells. However, the exact role of these cells is still under debate : does inflammation help protecting the brain against the disease or does it aggravate its progression?

In order to answer this question, research teams have analysed, among 96 subjects, microglial activity through the use of a new generation Tomography tracer by Emission of Positon (PET) at the Frédéric Joliot hospital center (Orsay, 91). At the same time, amyloid plaques were quantified by brain imaging in the same patients.

The results show not only that microglial cells activation is associated to the presence of amyloid plaques, but also that it is even more important as the disease is at an early stage. In order to measure its impact on the evolution of symptoms, patients were followed over two years. Patients with initially high microglial activity remained clinically stable overall, while patients with initially low microglial activity have unfavourably  progressed into a decline of autonomy. This is suggesting a protective role of the microglial inflammatory reaction on the evolution of the disease.

Moreover, this mechanism seems to appear at a preclinical stage, since the activation of microglial cells has been observed in asymptomatic subjects at risk of Alzheimer’s disease (namely that the presence of amyloid plaques has been observed, but with no effect on health). However, at a certain stage, when the disease progresses, inflammation could increase and then become deleterious.

This study, the first of its kind ever conducted in humans with brain imaging innovative technique, shows the beneficial and protecting role of the immune system during early stages of Alzheimer’s disease. It highlights the importance of diagnosing the disease early and opens new therapeutic prospects to slow down or even prevent its development.

* IMABio3 study focuses on the role of central and peripheral anti-amyloid inflammatory and immune reactions in early Alzheimer’s disease.

Reference : Early and protective microglial activation in Alzheimer’s Disease. A prospective study using [18F]DPA-714 PET imaging. Published in BRAIN. Lorraine Hamelin, Julien Lagarde, Guillaume Dorothée, Claire Leroy, Mickael Labit Robert A. Comley, Leonardo Cruz de Souza, Helene Corne, Luce Dauphinot, Maxime Bertoux, Bruno Dubois, Philippe Gervais, Olivier Colliot, Marie-Claude Potier, Michel Bottlaender, Marie Sarazin and the Clinical IMABio3.

Imabio3 Study on the role of central and peripheral anti-amyloid inflammatory and immune reactions in early Alzheimer’s disease: co-financed by the Roche Research and Translational Medicine Institute and the Ministry of Health, as part of a 2010 hospital clinical research program. It is promoted by Assistance Publique – Hôpitaux de Paris and will end in 2017.

Professor Marie Sarazin : Lead Investigator/coordinator of Imabio3 study, heads the Memory Neurology and Language unit at the Sainte Anne Hospital Center, Paris Descartes University, Sorbonne Paris Cité, Inserm UMRS 894.

Dr. Michel Bottlaender, UNIACT, NeuroSpin, and in Vivo Molecular Imaging Laboratory, UMR 1023, Frédéric Joliot Hospital Service, Biomedical Imaging Institute, Basic Research Department , Atomic and Alternative Energies Commission.

Dr. Lorraine Hamelin, neurologist and neuroscience PhD, a CEA/I2BM/Neurospin –  Paris Descartes University COLLABORATION under leadership of Professor Mary Sarazin and Dr. Michel Bottlaender. Supported by a doctoral fellowship funded by Alzheimer’s disease research foundation.

About AP-HP :

AP-HP is an internationally recognized university hospital center on a European scale. Its 39 hospitals welcome 7 million sick people every year : in consultation, emergency, during scheduled hospitalisations, or home-based hospitalisation. It provides public health service for all, 24/7, and it is both a duty and a pride. AP-HP is the first employer in Ile-de-France : 95 000 people – doctors, researchers, paramedical and administrative staff and workers – work there.

About CEA :

CEA is a public research organization involved in four areas : defence and security, nuclear energy, technological research for industry and basic research.
Based on the ability of its recognized expertise, CEA is involved in setting up collaborative projects with many academic and industrial partners. With its 16 000 researchers and collaborators, it is a major player in the European research area and has an international growing presence.

About the Sainte-Anne Hospital Center :

The institution, which will celebrate its 150 years of existence in 2017, is a hospital of national and international reference in the field of psychiatry and neuroscience. Multi-disciplinary hospital with 8 medical centers covering 7 adult sectors and 3 infanto-juvenile sectors in psychiatry, and the Neuro-Sainte-Anne Pole is dedicated to all brain pathologies. With 6 university hospital services, SAHC is the heart of a teaching and research network in partnership with Paris Descartes University. Since 2014, SAHC is managed jointly with EPS Maison Blanche and GPS Perray-Vaucluse, all 3 founding members of the Territory Community Hospital for Psychiatry in Paris. In scientific research, with an average of 140 scientific publications a year, the Sainte-Anne Hospital Center ranks 1st HC at the national level (apart from HUC and CCR) in terms of number of publications and 1 HC in terms of publication indicator (score SIGAPS). For further information :

About the Institut du Cerveau – ICM :

The Brain and Spine Institute (Institut du Cerveau – ICM) is a worldwide research center with no equivalent in the world, innovative both in its conception and its organization. Gathering together in a single location sick people, doctors and researchers, the objective is to enable rapid development of treatments for lesions of the nervous system in order to apply them to patients as rapidly as possible. Coming from a broad range of backgrounds and from all countries, the best scientists develop the most advanced research in this field.

About the Roche Institute and the Roche Basel Innovation Center :

Roche Institute is currently the only French institute fully dedicated to research partnership in life sciences.
Created in 2011, its main missions are :
• Being an interface with the scientific community ;
• Identifying innovative research projects aiming to establish high level scientific partnerships in areas of mutual concern ;
• Being a scientific local relay to the Roche Group research centers.
Roche Institute has led, since its creation, over a hundred research projects, representing an investment of more than 40 million euros.
Collaborative and multi-disciplinary research structure, Roche Institute is a scientific and biomedical innovation accelerator. It aims to transform basic research discoveries into clinical applications for the patient more quickly.
The Roche Basel Innovation Center Neuroscience Department develops drugs to treat serious neurological diseases such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, depression, autism, or Down syndrome.

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