New biomarker to diagnose Alzheimer’s disease in asymptomatic stages

Scientists have identified a new biomarker of Alzheimer’s disease in asymptomatic stages of the disease. It is a microRNA called miR-519a-3p and is directly related to the expression of the cellular prion protein (PrPC), which is deregulated in people who suffer from some neurodegenerative diseases such as Alzheimer’s.

The discovery was made in a recent study led by the Molecular and Cellular Neurobiotechnology group of the Institute of Bioengineering of Catalonia (IBEC) and the University of Barcelona (UB).

The search for biomarkers that are stable and easily detectable in biofluids, such as microRNAs, provides hope for the early detection of Alzheimer’s in its initial asymptomatic stages, which could help in the early diagnosis and treatment of this disease that affects more than 35 millions of people around the world.

It is known that the expression of some microRNAs is deregulated in patients with Alzheimer’s. However, this is the first time that this microRNA has been specifically linked to a decrease in cellular prion protein production during disease progression.

“Currently, tests to diagnose Alzheimer’s disease are usually carried out after the first symptoms appear, when there is already underlying cognitive impairment. We believe that the detection of this microRNA can help establish additional criteria for a more precise diagnosis in the initial phases of the disease,” explains José Antonio del Río, principal investigator at IBEC, professor at the Faculty of Biology and the Institute of Neurosciences ( UBneuro) from the University of Barcelona and co-leader of the study.

Furthermore, the work comparatively analyzes the presence of the biomarker in samples of other neurodegenerative diseases:

“If our goal is to use miR-519a-3p as a biomarker to detect Alzheimer’s dementia in hypothetically healthy people, it is key to ensure that its levels are not altered in other neurodegenerative diseases. In our study, we compared the levels of this biomarker in samples from other tauopathies and Parkinson’s, confirming that the changes in miR-519a-3p are specific to Alzheimer’s disease,” details Rosalina Gavín, senior researcher at IBEC, associate professor at the UB and UBneuro and co-leader of the study.

The team is advancing in its research, as indicated by Dayaneth Jácome, researcher in Del Río’s group and first author of the study: “the next step is the validation of miR-519a-3p as a biomarker in blood samples from different cohorts of patients, to begin using it in the clinical diagnosis of Alzheimer’s in peripheral samples.”

The researchers are members of the Network Research Center for Neurodegenerative Diseases (CIBERNED) in Spain.

This photograph, of freshly dead human tissue, taken using an optical microscope, shows a section of the frontal cortex of the brain of a person with late-stage Alzheimer’s disease. (Photo: Institute for Bioengineering of Catalonia (IBEC))

MicroRNAs: gene silencers

The amount of cellular prion protein changes during the progression of Alzheimer’s disease, showing higher levels in the early stages of the disease and decreasing as the disease progresses. Although the mechanism responsible for these changes is not known in detail, it has been observed that certain microRNAs bind to a specific region of the PRNP gene, which controls the expression of PrPC, decreasing it. Therefore, and based on comparisons of previous studies and computational analysis in various genomic databases, the researchers selected the microRNA miR-519a-3p for analysis.

The study is titled “miR-519a-3p, found to regulate cellular prion protein during Alzheimer’s disease pathogenesis, as a biomarker of asymptomatic stages.” And it has been published in the academic journal Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. (Source: IBEC)