Researchers from the Pasqual Maragall Foundation research center, the Barcelonaβeta Brain Research Center (BBRC), with the support of the “la Caixa” Foundation, have detected that the glial fibrillary acidic protein (GFAP, for its acronym in English) is a very accurate biomarker for diagnosing the early stages of Alzheimer's disease in the blood.
“The discovery will allow us to improve the diagnostic accuracy of the preclinical phase of Alzheimer's through a blood test, combining the detection of the GFAP biomarker with other recently discovered ones,” explains the Dr Marc Suarez-Calvet, principal investigator of the study and head of the Fluid Biomarkers and Translational Neurology group at the BBRC.
The results of the trial have been validated in nearly 900 participants from three cohorts dedicated to research into 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 of Frailty and Healthy Aging (CIBERFES) and the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN).
The role of GFAP in Alzheimer's disease
GFAP is a brain protein specific to astroglial cells. These cells are involved in different functional processes, such as supporting the activity of neurons and regulating the blood-brain barrier. When some type of brain damage occurs, a reaction of these cells takes place, called astrogliosis. This reaction attempts to contain brain damage and increases the expression of GFAP and other markers.
In the case of Alzheimer's disease, GFAP is a biomarker that is 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 in determining, more accurately and in a less invasive way, at what stage of Alzheimer's disease the affected person is.
“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 they allow us to differentiate individuals with or without amyloid pathology in the brain, which is the stage prior to the disease,” explains Marta Milà-Alomà, researcher of the study and member of the Fluid Biomarkers and Translational Neurology group at the BBRC.
Multicenter study
The results of the study were confirmed in people at different stages of the Alzheimer's disease continuum, participating in three independent international cohorts.
First, the researchers analysed blood samples from 387 people without cognitive impairment and at a certain risk of developing Alzheimer's, from the Alfa Study, launched in 2013 in Barcelona by the Pasqual Maragall Foundation and the 'la Caixa' Foundation. They also investigated the plasma of 300 asymptomatic people with cognitive impairment who are part of the TRIAD study, led by McGill University in Montreal. And finally, they analysed samples from 187 patients with cognitive impairment from the Lariboisière Hospital in Paris.
All assay samples were analyzed at the University of Gothenburg and quantified with high-precision technology (Simoa HD-X) using commercially available immunoassays.
New perspectives in research
The results of this international study add to the latest findings on 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 the tau protein, to detect the early stages.
As Dr. Suárez-Calvet, who now leads a prestigious European ERC Starting Grant in this field, explains, “In just two years, research into Alzheimer's biomarkers in the blood is advancing at such a pace that we are convinced that in the near future we will be able to detect the silent changes that occur in the brain with a simple blood test ordered by the family doctor. This will allow us to test a treatment before the neuronal damage is irreversible.”
The Pasqual Maragall Foundation is currently launching a translational laboratory equipped with technologies such as those used in this study, in order to bring cutting-edge tools for Alzheimer's disease research to Spain and make them available to the scientific community and patients.
