Researchers develop blood test panel for early Alzheimer’s detection

Researchers at the Federal University of São Carlos (UFSCar) in the state of São Paulo, Brazil, are developing a panel of biomarkers for the early detection of Alzheimer's disease and for distinguishing it from other types of dementia using blood tests. The research project is supported by FAPESP and is based on the genotype analysis of 500 volunteers with and without the disease.

One of the most recent findings by the research group, published in the journal Neurobiology of Aging, was the identification of a rare genetic alteration related to Alzheimer's disease that is also associated with high levels of the ADAM10 protein. The study examined 85 individuals with cognitive impairment and the genetic condition, all of whom had high levels of the protein in their blood.

The protein is known among scientists for its role in cleaving, or breaking down, the beta-amyloid precursor protein. This prevents the formation of plaques in the brain, which is a hallmark of Alzheimer's disease.

ADAM10 is an old candidate biomarker for Alzheimer's disease that in recent years has gained prominence due to advances in ultrasensitive equipment that allows these molecules to be detected at very low concentrations in the blood plasma."

Márcia Regina Cominetti, from the Biology of Ageing Laboratory (LABEN-UFSCar) and one of the project's coordinators

The study found that the genetic condition involving alterations in the E4 allele of the APOE gene could result in an increase in inactive ADAM10 molecules in the blood. Consequently, the amount of active molecules would decrease, reducing their ability to inhibit the formation of beta-amyloid plaques in the brain.

Complex disease

Alzheimer's disease is the leading cause of dementia worldwide, affecting over 35.6 million people. Not only is there no cure, but diagnosis remains a major challenge for medicine. The earlier it is identified, the greater the chance of delaying the onset of symptoms. This is because, until now, reversing the neurodegenerative process has only been possible in the early stage of the disease, known as mild neurocognitive impairment. This stage is characterized by cognitive decline without significantly affecting the individual's functionality.

In this context, UFSCar researchers are developing prognostic blood tests based on ADAM10 that can identify individuals with mild cognitive impairment who are at a higher risk of developing Alzheimer's disease.

"Our studies indicate that not only in the case of this rare condition but also in other causes of Alzheimer's disease ADAM10 acts in a pathway prior to the formation of beta-amyloid plaques. With this, it's possible, if everything goes as our hypothesis predicts, that it could be a prognostic marker, indicating, before the formation of these pathological milestones, whether or not the person has a chance of developing the disease," says the researcher.

Cominetti points out that, currently, the detection of beta-amyloid plaques in the brain and hyperphosphorylated tau protein (another hallmark of Alzheimer's disease) is highly accurate for diagnosis. "However, differentiating one dementia from another is still a major challenge. In this sense, a combination of biomarkers could, for example, make broader population screening possible through blood tests," he says.

In partnership with the Chemistry and Gerontology departments at UFSCar, the researchers have developed a sensor that uses ADAM10 levels in the blood to distinguish between healthy older adults and those with Alzheimer's disease. The test is currently being validated through studies with 500 volunteers.

"We're moving towards finding prognostic markers for the disease. Many people wonder why they're looking for a diagnosis if there's no cure for Alzheimer's yet. The fact is that we're working in the long term. At some point, a cure may appear and then it'll be extremely important to have a diagnostic method like the one we're proposing to develop," he says.

Another important aspect of the project, Cominetti notes, is the construction of a genetically diverse database that also considers risk factors for Alzheimer's, such as education level, income, and quality of life. "We've completed the genetic sequencing of the 500 volunteers, creating a database without equal in the world. As well as reflecting Brazil's genetic variability, the database is the result of a population that has distinct characteristics from the Global North, where most research is conducted. This is important because it's known that the relevance of risk factors for Alzheimer's can vary between rich and poor regions," explains Cominetti.