🧠 Detecting Alzheimer's much earlier through a simple blood test

Once the diagnosis is made, it is too late to reverse Alzheimer's disease. That is why detecting the first signs of cognitive decline is crucial. A team from Université Laval has examined biomarkers present in the blood and identified two promising molecules, according to a study published in Alzheimer's & Dementia.

Exploring the metabolic pathway

The scientists studied molecules associated with metabolic diseases, such as type 2 diabetes or hypertension, which are linked to a greater risk of developing Alzheimer's. "We wanted to see how these metabolic biomarkers behaved in relation to cognitive changes," explains Frédéric Calon, a professor at the Faculty of Pharmacy and researcher at the CHU de Québec-Université Laval Research Center, who led the research.

Some blood biomarkers, including the phospho-tau protein, are already used clinically for the diagnosis of Alzheimer's, but their presence is detected when the disease is already at an advanced stage, points out Caroline Dallaire-Théroux, a clinical-research resident, neurologist, and first author of the study. "Our goal was to identify indicators that emerge long before the first symptoms, ideally up to 20 years before the disease. Since they are measurable in the blood, it is less invasive than sampling cerebrospinal fluid, in which the brain is bathed, and more accessible than using brain imaging."

For the study, the team analyzed data from the Consortium for the Early Identification of Alzheimer's Disease-Quebec (CIMA-Q). The 290 participants, aged 65 and over, were divided into four groups: healthy, with subjective cognitive decline, with mild cognitive impairment, and with Alzheimer's disease. "People with subjective decline express a concern about their cognitive ability," specifies Professor Calon. The metabolic status of each person was assessed using measurements such as waist circumference and blood glucose.

Markers with different behaviors

In the people from the four groups, the scientists measured three biomarkers related to metabolism: IGFBP2, associated with insulin sensitivity; FGF21, linked to glucose regulation; and adiponectin, connected to lipid and glucose regulation. The level of these markers in the blood was then associated with cognitive status and the level of phospho-tau. Contrary to expectations, the three molecules did not behave in the same way.

The most promising metabolic biomarker is IGFBP-2. Its level decreases in the presence of a metabolic disorder, but increases as cognitive impairments progress. Its behavior is then similar to that of the phospho-tau protein. The FGF-21 molecule increases both for metabolic and cognitive disorders, but the correlation is weaker. In the case of adiponectin, the team did not see an association with cognitive status.

Distinguishing profiles and anticipating disease progression

With metabolic blood markers, scientists hope to distinguish different profiles of people affected by Alzheimer's, particularly those for whom metabolism plays a more significant role. "These individuals might perhaps benefit from personalized treatment. Metabolic diseases have a well-equipped therapeutic arsenal; it would be interesting if these advances could be transposed to Alzheimer's disease," emphasizes Frédéric Calon.

The team now wishes to study the evolution of biomarkers over time. "The advantage of the CIMA-Q cohort is that it is followed over several years. We could see if the level of molecules allows us to predict the trajectory of the disease," adds Caroline Dallaire-Théroux.

Studies in mice could also help better understand the precise role of IGFBP2 and FGF21 molecules in the brain and find new therapeutic strategies.