A biomarker has been identified in the blood that allows the early stages of Alzheimer's disease to be detected precisely

Researchers at the Pasqual Maragall Foundation's research centre, the Barcelonaβeta Brain Research Center (BBRC), with the support of the "la Caixa" Foundation, have detected that glial fibrillary acidic acidic protein (GFAP) is a very precise biomarker for diagnosing the early stages of Alzheimer's disease in the blood.

"The finding will improve the diagnostic accuracy of the preclinical phase of Alzheimer's disease through a blood test, combining the detection of the GFAP biomarker with other recently discovered biomarkers," explains Dr Marc Suárez-Calvet, principal investigator of the study and head of the Fluid Biomarkers and Translational Neurology group at the BBRC.

The trial results have been validated in nearly 900 participants from three cohorts dedicated to Alzheimer's prevention research. 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 involved 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 of Medical Research (IMIM), the CIBER of Fragility and Healthy Ageing (CIBERFES) and the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN).
 

GFAP is a brain protein specific to astroglia cells. These cells are involved in different 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 attempts to contain the brain damage and increases the expression of GFAP and other markers.

GFAP is a brain protein specific to astroglia cells. These cells are involved in different 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 attempts to contain the 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 a lumbar puncture of 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 for determining, more accurately and less invasively, where a person is in Alzheimer's disease.

"We have seen that the levels of the biomarker GFAP 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 Biomarkers in Fluids and Translational Neurology group at the BBRC.
 

The results of the study have been 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 alterations and with a certain risk of developing Alzheimer's disease, from the Alfa Study, promoted in 2013 in Barcelona by the Pasqual Maragall Foundation and the "la Caixa" Foundation. They also investigated plasma from 300 asymptomatic people with cognitive impairment who are part of the TRIAD study, led at McGill University in Montreal. And finally, they analysed samples from 187 patients with cognitive impairment at the Lariboisière Hospital in Paris.

All assay samples were analysed at the University of Göteborg and quantified with high-precision technology (Simoa HD-X) using commercially available immunoassays.
 

The results of this international study add 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 early stages.

As Dr Suárez-Calvet, who is now leading a prestigious European ERC Starting Grant in this field, explains, "in just two years, research in the field of 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 occurring in the brain with a simple blood test requested by the family doctor. This will allow us to try treatment before the neuronal damage becomes irreversible".

The Pasqual Maragall Foundation is currently setting up a translational laboratory equipped with technologies such as the one used in this study, in order to bring state-of-the-art Alzheimer's disease research tools to Spain and make them available to the scientific community and patients.
 

Andréa L. Benedet; Marta Milà-Alomà; Agathe Vrillon; Nicholas J. Ashton; Tharick A. Pascoal; Firoza Lussier; Thomas K. Karikari; Claire Hourregue; Emmanuel Cognat; Julien Dumurgier; Jenna Stevenson; Nesrine Rahmouni; Vanessa Pallen; Nina M. Poltronetti; Gemma Salvadó; Mahnaz Shekari; Gregory Operto; Juan Domingo Gispert; Carolina Minguillon; Karine Fauria; Gwendlyn Kollmorgen; Ivonne Suridjan; Eduardo R. Zimmer; Henrik Zetterberg; José Luis Molinuevo; Claire Paquet; Pedro Rosa-Neto; Kaj Blennow; Marc Suárez-Calvet; Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum, JAMA Neurol. doi:10.1001/jamaneurol.2021.3671.

Every 3 seconds a new case of dementia  is diagnosed in the world, and it is estimated that there are currently 50 million people affected, in most cases due to Alzheimer's disease. This figure translates into more than 900,000 people in Spain. With life expectancy on the rise, if no treatment is found to prevent or slow the course of the disease, the number of cases could triple by 2050, reaching epidemic proportions, as the latest World Alzheimer Report 2018 published by Alzheimer's Disease International points out.

El Barcelonaβeta Brain Research Center (BBRC) es el centro de investigación de la Fundación Pasqual Maragall, impulsado por la Fundación ”la Caixa” desde su creación, dedicado a la prevención de la enfermedad de Alzheimer y al estudio de las funciones cognitivas afectadas en el envejecimiento sano y patológico.
La Fundación Pasqual Maragall es una entidad sin ánimo de lucro que nació en abril de 2008, como respuesta al compromiso adquirido por Pasqual Maragall, exalcalde de Barcelona y expresidente de la Generalitat de Catalunya, cuando anunció públicamente que le habían diagnosticado la enfermedad de Alzheimer. La misión de la Fundación es promover la investigación para prevenir el Alzheimer y ofrecer soluciones que mejoren la calidad de vida de las personas afectadas y la de sus cuidadores.