Alzheimer's is the most common form of dementia in old age. And it is also one of the diseases that is present in Navarre households (according to the last recorded census, in Navarra there are more than 5,000 people with a confirmed diagnosis). Due to the increase in life expectancy of the population, its incidence is rising considerably. In fact, as the World Health Organization points out, 10 million new cases are diagnosed every year worldwide.

There is currently no treatment capable of preventing or curing the disease, which is why it is necessary to insist on the urgent need for research into effective therapies to treat the disease or, at least, to slow it down development.

In recent years, several studies have been carried out programs of study to identify the factors involved in the process of healthy aging. Interestingly, approximately one third of people over 75 years of age who die without showing signs of dementia have typical Alzheimer's lesions (senile plaques and neurofibrillary tangles) in their brains. This indicates that some individuals "escape" the disease by keeping their report intact, despite developing characteristic signs in their brains. They are called "resilient" individuals.

Most of these programs of study conclude that the "cognitivereservation " and a certain lifestyle (exercise, training academic, sociocultural activities, per diem expenses...) are possible protective factors, responsible for resistance to developing the disease. However, none of these studies have paid attention to the molecular mechanisms involved in this resilience. At the laboratory of Alzheimer's Disease of the Cima University of Navarra we are studying these factors in depth and have found that, as in humans, approximately 20% of the animal models of the disease retain their learning capacity despite having severe pathology in their brains.

The study of these resilient animals has led us to identify a new potential therapeutic target for Alzheimer's disease: the PLA2G4E protein. Specifically, the brains of the resilient models showed higher levels of this enzyme than the impaired models report, and similar to healthy animals. This finding indicated that PLA2G4E was one of the protective factors preventing the loss of report associated with Alzheimer's disease.

To validate the therapeutic potential of this new target, we generated a viral vector that is administered by gene therapy in the hippocampal neurons of our disease models. The hippocampus is the region of the brain responsible for the acquisition of new memories and is one of the first regions affected in Alzheimer's disease. Two months after administration of the therapeutic virus, we observed that, indeed, overexpression of PLA2G4E in hippocampal neurons restored report in diseased animals mimicking human disease. These data have been recently published in the journal "Progress in Neurobiology", one of the leading journals in the field of neuroscience.

In general, we can highlight that identifying resilience markers allows the identification of new therapeutic targets, which is fundamental in the current context, in which clinical trials for Alzheimer's disease have repeatedly failed. Furthermore, analysis of this subject of resilience markers could help predict whether or not an individual will develop dementia.

The research knows no borders and many international multicenter programs of study are currently underway, some with promising clinical applications. But to advance in the search for an effective treatment that cures or, at least, slows down the development of Alzheimer's disease, it is essential to have economic resources. Institutions cannot look the other way, but must invest in the biomedical field. An investment that helps to retain the talent of our scientists.

Today, especially on World Alzheimer's Day, our attention is focused on patients, their caregivers and family associations, who give so much visibility to the needs of the patient. They are the impetus that encourages us to continue day by day in our scientific activity and to raise our spirits when the scientific results do not go as planned. To them and to so many donors (individuals and companies) who support the research of Alzheimer's disease goes our most sincere thanks. Because without science there is no future.