ADAPTED – Alzheimer’s Disease Apolipoprotein Pathology for Treatment Elucidation and Development

Fundació ACE–Barcelona Alzheimer Treatment & Research Center has been selected by the European consortium Innovative Medicines Initiative (IMI) to lead the ADAPTED research project (Alzheimer’s Disease Apolipoprotein Pathology for Treatment Elucidation and Development). In view of the lack of drugs capable of slowing the progression of the disease, ADAPTED opens up a new line of research into the origins of Alzheimer’s disease. Its object of study pursues a systematic approach to APOE as a potential therapeutic target. The APOE gene is a well-known risk factor for the disease, but to date it has received less attention from researchers than other targets. The APOE gene encodes a protein involved in cholesterol transport. Carrying the genetic variant known as APOE4 is one of the most important risk factors for developing Alzheimer’s disease. Although this has been known for more than twenty years, the molecular mechanisms underlying this association remain unknown, as it has so far received less attention from the scientific community. Specifically, the role of the APOE gene in the onset of Alzheimer’s disease is not yet understood. This lack of understanding of its function has meant that, until now, this gene has largely been overlooked in the search for treatments.

With a budget of €7 million, the aim of this study—which expands the traditional lines of Alzheimer’s research and is coordinated by Fundació ACE—is to identify how APOE increases the risk of developing Alzheimer’s disease and, in this way, to enable the development of new drugs. With ADAPTED, Fundació ACE becomes the first Spanish institution to be selected to coordinate, simultaneously, two European research projects on the origins of Alzheimer’s disease. It should be recalled that IMI has also selected the institution to coordinate another European study aimed at identifying effective mechanisms for the early detection of Alzheimer’s disease (MOPEAD).

Gene present in 45% of cases

The APOE gene is present in more than 45% of Alzheimer’s cases and, for this reason, according to Dr. Agustín Ruiz, Head of Research at Fundació ACE, “understanding the function of APOE is a major scientific challenge.” Ruiz notes that “if the project is successful, the treatment and prevention of Alzheimer’s disease will enter a completely new era of drug and therapy identification.” Currently, through DNA analysis, it is possible to observe the behavior of this gene and identify an individual’s percentage risk of developing Alzheimer’s disease. For example, an individual with two copies of the epsilon 2 allele of the gene would have a 6% probability of developing the disease. However, someone with two copies of another variant of the gene (the epsilon 4 allele) would have a risk of over 50%. Since its earliest stages, the accumulation of the beta-amyloid protein in the brain has been considered one of the causes of the onset of the disease; this hypothesis will continue to be explored through protein research, in parallel with the genetic research opened up by the new study.