UABDivulga - Barcelona recerca i innovació

Alzheimer’s disease is one of the leading causes of age-related disability, and a key challenge is to detect it before extensive neuronal damage occurs. In this work, we present a liquid-biopsy–based diagnostic method using plasma exosomes: small vesicles that circulate in the bloodstream and carry molecular information from their cells of origin. The difficulty is that plasma contains exosomes from many different tissues; therefore, brain-origin exosomes must be selectively enriched before measuring a biomarker.

Our strategy combines magnetic selection with a portable electrochemical readout. First, we use a neuronal-origin marker as an “address tag” to discriminate, through magnetic separation, brain-derived exosomes from the broader plasma exosome background. To do this, we functionalize magnetic particles with an antibody against neuroligin-3 (NLGN3), a protein associated with brain synapses. When mixed with plasma, these magnetic particles preferentially capture exosomes bearing signals consistent with brain origin and allow rapid isolation using a magnet, in a simple way that is compatible with everyday-use environments.

Once this enriched fraction is isolated, our portable biosensor quantifies a biomarker relevant to Alzheimer’s disease: beta-secretase 1 (BACE-1), a key enzyme involved in processes associated with amyloid-beta formation. The device relies on screen-printed electrodes and single-use cartridges, and the technology is patented. The system converts a specific enzymatic reaction into a measurable electrical signal, providing an objective readout that can be automated. In addition, the reader is portable and battery-operated, reinforcing its use beyond highly specialized laboratories with compact equipment and straightforward operation.

We are currently expanding the study to larger cohorts, and preliminary results are very promising regarding the system’s ability to capture brain-origin exosomes and generate consistent BACE-1 signals with the portable biosensor. This approach is particularly relevant because it points to detection at very early stages of the disease, before extensive neuronal damage occurs and when clinical changes may still be subtle. Our goal is to advance toward a tool that supports screening and follow-up from a simple blood sample, contributing to earlier detection and more personalized medicine.