Ten years ago, the Pasqual Maragall Foundation had the intuition that Alzheimer's had to be studied before it manifested in its most fulminant phase, as is done with other diseases like cancer. The Barcelona center went against the current and it has been very difficult to convince the scientific community that its thesis made sense, considering that most trials are done on already sick patients.
On its tenth anniversary, the foundation has proven they were right. The journal Nature Medicine has just published the results of a study that validates a pioneering mechanism to detect Alzheimer's in the blood of patients who do not yet have visible symptoms of the disease, but in whom the brain has already begun to alter. The study was led by the Barcelonaβeta Brain Research Center (BBRC), a research center of the Pasqual Maragall Foundation; the Hospital del Mar Medical Research Institute (IMIM-Hospital del Mar), and the University of Gothenburg.
"We are not discovering a treatment, but we are facilitating the ability to develop one in the future," explains Dr. Marc Suárez-Calvet, a researcher at the BBRC and IMIM-Hospital del Mar. Currently, it is difficult to find patients in the preclinical phase of Alzheimer's, which prevents more clinical trials from being conducted to test possible medications or better understand the disease.
The research led from Barcelona has confirmed that, in the plasma of cognitively healthy patients, the presence of two proteins is detected that grow considerably when another protein, amyloid, begins to accumulate in the brain, which is what determines the onset of Alzheimer's. Once amyloid begins to concentrate, the person is very likely to end up developing the pathology, although many years may pass for this to happen, with the first symptoms beginning to manifest up to 20 or 30 years later.
The proteins validated by the study are p-tau231 and p-tau217. The first blood biomarker, developed by the BBRC and the University of Gothenburg, has been the one that has shown the best performance in detecting the first signs of amyloid accumulation in the brain. A biomarker is understood as any substance that provides information about a disease, such as those contained in a blood test or a urine sample.
Until now, to include patients in clinical trials for Alzheimer's, they had to undergo a lumbar puncture, the most common and conclusive way to diagnose it. Through this test, the accumulation of amyloid in the brain is confirmed. The problem is that it is an expensive mechanism that cannot be repeated very often, whereas blood biomarker analysis is an economical and non-invasive procedure that can help in the diagnostic process of this pathology. With the identification of p-tau231 and p-tau217 proteins, it is possible to refine who needs to undergo a lumbar puncture, ruling out patients and ensuring greater effectiveness in triage.
In this regard, Suárez-Calvet emphasizes that the new mechanism will reduce the recruitment time of patients in clinical trials for Alzheimer's prevention, as well as increase the level of participation in these studies and the variety of profiles included.
Precisely, the main study developed by BBRC to investigate Alzheimer's in the preclinical phase, the Alfa study, collected samples from 3,000 healthy people ten years ago, most of them daughters of Alzheimer's patients. From that initial sample, the research focused on 400 patients, the Alfa+ subgroup, following them more intensively to see how the pathology was progressing, performing tests such as lumbar punctures and visiting them regularly. The main reason for this limitation was that the supervision process could not be done with everyone due to resource and complexity issues. Now, with the validation of blood biomarkers, this subgroup can be expanded, Suárez-Calvet advances, and new clinical trials can be undertaken. All of this, with the purpose of increasing the critical mass and facilitating the discovery of new advances in research to prevent Alzheimer's.
The discovery will reduce the recruitment time of patients in clinical trials for Alzheimer's prevention, as well as increase the level of participationFor this, Suárez-Calvet stresses, it will be essential the laboratorythat the BBRC has recently launched, specialized in the study of biomarkers to detect Alzheimer's. Located on the first floor of the building that houses the Pasqual Maragall Foundation and the BBRC, on the Ciutadella campus of Pompeu Fabra University (UPF), it is finishing receiving the necessary equipment and hiring researchers. The laboratory was inaugurated in spring, but it is expected to reach cruising speed starting in September. Even more so with the international discovery that the BBRC has just announced.