The scientific publications on Alzheimer’s disease follow : more than 17, 000 since the beginning of the year. But those who are talking are more rare. This is the case of a study very compelling published on the 21st of June in the journal Neuron : it highlights the presence of virus in the brains of patients.
Alzheimer’s disease affects over a million people in France, and approximately 40 million people in the world. Because of the aging of the population, the number of cases is increasing and strong growth is expected in the next two decades. This disease develops slowly and progressive disruption of the functioning of memory and other cognitive functions, and loss capacity of the patient to achieve the routine things of daily life ; also, it leads to a dependence vis-à-vis the surroundings. It has other consequences such as behavioral disorders, nutritional disorders, falls, or depressive states, as well as a decrease in life expectancy compared to people of the same age who does not have this disease.
A pathology which remains a mystery
in Spite of intense research, the cause or causes of Alzheimer’s disease are not clarified, and this has significantly limited the development of effective therapeutic strategies. Since the observations of Alois Alzheimer at the beginning of the Twentieth century, the search for the origin of the disease has focused on the formation of brain lesions observable under the microscope : amyloid plaques and clumps neurofibrillary.
The amyloid plaques are formed by the deposition of a small molecule called a peptide A-Beta or amyloid-beta peptide. These peptides are joined to each other to form deposits inter-cellular. They come from a larger protein that is normal and present in the membrane of the neuron, and is called ” APP ” for ” amyloid precursor protein “. In normal conditions, this protein ” APP ” is turned off in order to form proteins which are small, non-toxic, some of which could play a useful role for the neurons. In Alzheimer’s disease, the protein ” APP ” is cut in the wrong place. Influenced by a number of enzymes, the process leads to the formation of a peptide beta-amyloid that are too important. In aggregating to form amyloid plaques that are believed to play a crucial role in the formation of symptoms and the development of Alzheimer’s disease.
However, this design is called the hypothesis amyloid is currently being seriously questioned, because it has led for the moment to an impasse on the search for drugs that can halt the disease. Indeed, molecules designed to prevent the formation of plaques or even remove those already formed have not resulted in clinical benefits for patients. As for the cluster neurofobrillaires, the development of a pharmacological strategy to modulate only the beginning and it is too early to tell if it will pay off.
A new hypothesis in the original
In this context, the work published in Neuron has been noticed because he raises a very credible hypothesis of the track is infectious as a possible origin of the disease. The researchers of the university of Mount Sinai in New York conducted a study which consisted in genomic analyses of DNA and RNA in samples from brains of patients with Alzheimer obtained post-mortem and to compare the results to those obtained in samples from brains of people who are not sick. The research and quantification of viral genome were carried out in a systematic manner by means of specialized platforms (especially genomics and transcriptomics), followed by a bioinformatics analysis of complex results.
unexpectedly, the results showed that the samples from diseased Alzheimer’s were the most frequent sequences of viral genetic material, including viruses of the family of Herpes human virus type 6 and type 7. The researchers have been very cautious since they have undertaken to verify if there were similar results in the samples of two other banks of brains from independent cohorts. The presence of the same viral genomes has been found more frequently in the brains of patients of Alzheimer of the other two cohorts.
This association is not proof of a causal relationship between the presence of the viral material and the development of the disease. For example, one could imagine that Alzheimer’s disease makes patients more vulnerable vis-à-vis these viruses and that it is therefore a consequence rather than a cause. Also to explore the hypothesis of causality, the authors of this study explored possible relationships between these viruses and amyloid proteins that are deposited in the brain of patients with Alzheimer. In mice genetically modified to develop these plaques, they have confirmed that these viruses could lead to an increase in the density of amyloid plaques.
in addition, the amyloid plaques seem to slow the growth of herpes virus. We see, therefore, is to draw a new hypothesis concerning the origin of Alzheimer’s disease, in which amyloid plaques are a element reaction, even protective, vis-à-vis the aggression neural by viruses. This would explain the failure to plan clinical treatments that were aimed at reducing the production of the plates or even remove the brain of the sick.
The disease be transmitted ?
A possible viral origin of Alzheimer’s disease raises of course the question of its transmission inter-human. These results, however, should not worry about the carers or the professionals who care for Alzheimer’s patients. The epidemiology of the disease is not like in any case to that of communicable diseases, and if these viruses play a role, it is probably a contamination in childhood is very frequent : it is estimated that 80% or 90% of the population has been in contact with these herpes virus in childhood.
What is special in these results, it is not so much the virus itself, its presence at the level of the brain and its persistence as long. This could present some analogies with the pathophysiology of shingles, another disease associated with a herpes virus of another type (causes chicken pox). The infection occurs in childhood and the virus remains several decades in the ganglia of the nervous system, until a time that is conducive to the reactivation responsible for the herpes zoster acute.
Unquestionably this study opens a new avenue of research and we can expect to see in the coming years the development of new therapeutic approaches for Alzheimer’s disease, for example, new types of vaccines, or clinical trials with antiviral drugs active on the herpes virus.
*Joël Belmin professor of geriatrics at the university of the Sorbonne.