Researchers at the Pasqual Maragall Foundation's research center, the Barcelonaβeta Brain Research Center (BBRC), with the support of the “la Caixa” Foundation, have detected that the glial fibrillar acid protein (GFAP) is a very accurate biomarker for diagnosing in blood the early stages of Alzheimer’s disease.
"The finding will improve the diagnostic accuracy of the preclinical phase of Alzheimer's through a blood test, combining the detection of the GFAP biomarker with others recently discovered", says Dr. Marc Suárez-Calvet, principal investigator of the study and head of the group of Biomarkers in Fluid and Traslational Neurology at the BBRC.
The results of the trial were validated in nearly 900 participants from three cohorts dedicated to research in Alzheimer’s prevention. One of the cohorts is the Alfa Study, promoted by the ‘la Caixa’ Foundation in Barcelona.
The research has been published in the journal JAMA Neurology, and has had the collaboration of researchers from the University of Gothenburg, McGill University in Montreal, the University of Paris, the Lariboisière Fernand-Widal Hospital in Paris, the Hospital del Mar and the Hospital del Mar Institute for Medical Research (IMIM), the CIBER for Fragility and Healthy Aging (CIBERFES) and the CIBER for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN).
The role of GFAP in Alzheimer's disease
GFAP is a brain protein specific to astroglia cells. These cells are involved in various functional processes, such as supporting the activity of neurons and regulating the blood-brain barrier. When some kind of brain damage occurs, a reaction of these cells takes place, called astrogliosis. This reaction is to contain brain damage and elevate the expression of GFAP and other markers.
In the case of Alzheimer’s disease, GFAP is a biomarker that was usually measured in the cerebrospinal fluid, after performing a lumbar puncture on the patient. The novelty of this study is that it shows that GFAP measured in blood plasma is better than that measured in cerebrospinal fluid to determine, more accurately and less invasively, at what point in Alzheimer's disease the person is affected.
"We have seen that the levels of the GFAP biomarker are higher in people who are in the asymptomatic phase of Alzheimer's, and that allow us to differentiate individuals with or without amyloid pathology in the brain, which is the stage prior to disease ”, explains Marta Milà-Alomà, researcher of the study and member of the group of Biomarkers in Fluid and Traslational Neurology of the BBRC.
The results of the study have been confirmed in people who are in the different phases of the continuum of Alzheimer's disease, and who participate in three independent international cohorts.
First, the researchers analyzed the blood samples of 387 people without cognitive impairments and with a certain risk of developing Alzheimer's, from the Alfa Study, which was promoted in 2013 in Barcelona by the Pasqual Maragall Foundation and the 'La Caixa' Foundation. They also investigated the plasma of 300 asymptomatic and cognitively impaired people who are part of the TRIAD study, led at McGill University in Montreal. And finally, they analyzed samples from 187 patients with cognitive impairment at the Hospital Lariboisière in Paris.
All tests of the assay were analyzed at the University of Gothenburg, and quantified using high-precision technology (Simoa HD-X) using commercially available immunoassays.
New perspectives in research
The results of this international study are in addition to the latest findings of blood biomarkers to detect Alzheimer's disease. In November 2020, the same team led by Dr. Suárez-Calvet at the BBRC identified other biomarkers, in this case of the tau protein, to detect the initial phases.
As explained by Dr. Suárez-Calvet, who also leads a prestigious European ERC Starting Grant in this field, “in just two years, research in the field of biomarkers of Alzheimer's in the blood is advancing at such a pace that we are convinced that in the future next we will be able to detect the silent changes that occur in the brain with a simple blood test requested by the GP. This will allow us to try treatments before the neuronal damage is irreversible”.
The Pasqual Maragall Foundation is currently setting up a traslational laboratory equipped with technologies such as the one used in this study, in order to be able to bring state-of-the-art tools to Spain in the research of Alzheimer's disease and put them in the service of the scientific community and patients.