ExoSens-PoC. Enhancing tests for the early diagnosis of Alzheimer’s disease.
Project reference
PDC2022-133363-I00
Programme and call for tender
Proyectos de Prueba de Concepto 2022
Principal Investigator
Isabel Pividori /Mercè Martí (CoIP)
Duration
Dic 2022 – Dic 2024
Alzheimer’s Disease (AD) is the major single cause of dementia. It courses with a long prodromal period, which difficult the identification of patients in early stages in which they might benefit from disease modifying treatments. Existing diagnostic tools such as brain imaging or cerebrospinal fluid biomarkers are expensive and invasive procedures, limiting their appeal to patients. Exosomes, small extracellular vesicles secreted by most cell types, have been recently proposed as carriers of biomarkers for many non-transmissible diseases as their cargo reflects cellular processes happening in the cell of origin. In the context of AD, they have been shown to be carriers of AD-related molecules. These vesicles can be found in many biofluids, such as plasma, therefore making them a suitable target for non-invasive biomarker research. ExoSens-PoC proposal addresses the development of a Proof-of-Concept/Point-of-Care (PoC) test for the early identification of individuals at risk of AD in plasma. Such a test can be used both in low resource settings where current technologies are not available, and in high-income countries at community and primary-care level to dramatically improve turnaround times for results and reduce costs. The device is rapid and inexpensive, requiring minimal handling, and can easily be introduced into the general practitioner’s armory for ambulatory screening of AD and risk-stratification of the patients, increasing thus its valorization.
Prof. Isabel Pividori, experts in the Diagnostic Tests based on exosomes will partner with ACE foundation/ Institut Català de Neurociències Aplicades and EureCat in this acceleration phase, to build a reliable, scalable, and secure product faster and at the same time, ensuring compliance with the EU Regulation.
This two year project is funded by the European Union NextGenerationEU.
Summary of the results
El proyecto ExoSens-PoC ha desarrollado una nueva herramienta de diagnóstico precoz para la enfermedad de Alzheimer, basada en un biosensor electroquímico capaz de detectar biomarcadores específicos en exosomas neuronales aislados a partir de muestras de plasma. Esta tecnología permite clasificar a los pacientes según su perfil neurodegenerativo, en coherencia con los marcos diagnósticos actuales, de forma rápida, mínimamente invasiva y accesible.
Detectar la enfermedad de Alzheimer en muestras de suero o plasma representa un avance estratégico clave en el campo de las enfermedades neurodegenerativas. A diferencia de las técnicas convencionales basadas en líquido cefalorraquídeo o neuroimagen —más costosas, invasivas o inaccesibles—, el análisis de sangre abre la puerta a cribados poblacionales, monitorización longitudinal y diagnóstico en fases preclínicas, cuando aún es posible intervenir terapéuticamente.
Durante el desarrollo del proyecto se diseñó un sistema que integra separación inmunomagnética y detección electroquímica directa, sin necesidad de procesamiento complejo ni equipamiento especializado. Se construyó y validó un prototipo portátil de bajo coste, demostrando su utilidad en condiciones clínicas reales y su potencial para ser utilizado en atención primaria o entornos con recursos limitados. Los biomarcadores empleados en esta plataforma también podrían adaptarse a otros formatos diagnósticos ampliamente utilizados en el sistema sanitario, como ELISA o quimioluminiscencia, facilitando su escalabilidad.
Gracias a ExoSenSPoC, el sistema avanzó desde un nivel de madurez tecnológica TRL 3 (prueba de concepto en laboratorio) hasta TRL 6 (prototipo validado con muestras clínicas reales en entorno relevante). La tecnología ha sido protegida mediante patente internacional, como paso previo a su transferencia al sector biomédico.
En conjunto, ExoSens-PoC demuestra que es posible acercar el diagnóstico temprano del Alzheimer al punto de atención, mejorando la equidad en el acceso a pruebas diagnósticas, y abriendo nuevas vías para la prevención, la investigación clínica y el seguimiento personalizado de los pacientes.
The ExoSens-PoC project has developed a novel tool for the early detection of Alzheimer’s disease, based on an electrochemical biosensor capable of detecting specific biomarkers in neuronal exosomes isolated from plasma samples. This technology enables the stratification of patients according to their neurodegenerative profile, in line with current diagnostic frameworks, in a rapid, minimally invasive, and accessible way.
Detecting Alzheimer’s disease using serum or plasma samples represents a key strategic breakthrough in the field of neurodegeneration. Unlike conventional techniques based on cerebrospinal fluid (CSF) analysis or neuroimaging—which are often invasive, expensive, or inaccessible—blood-based diagnostics open the door to population-level screening, longitudinal monitoring, and early diagnosis at preclinical stages, when therapeutic intervention is still possible.
Throughout the project, the team designed a system integrating immunomagnetic separation with direct electrochemical detection, requiring no complex sample processing or specialized equipment. A low-cost, portable prototype was developed and validated under real clinical conditions, demonstrating its potential for use in primary care settings or resource-limited environments. The same biomarkers could also be incorporated into other well-established diagnostic formats, such as ELISA or chemiluminescence-based assays, facilitating broader adoption.
As a result of this work, the technology progressed from TRL 3 (experimental proof of concept in the lab) to TRL 6 (prototype validated in a relevant clinical environment with real samples). The system has been protected through international patent filing, and a freedom-to-operate analysis was completed as a prerequisite for future biomedical transfer.
In summary, ExoSens-PoC shows that bringing early Alzheimer’s diagnosis to the point of care is feasible, with the potential to improve diagnostic equity and open new pathways for prevention, clinical research, and personalized patient management.
Publications
2024
Peptide-based biosensing approaches for targeting breast cancer-derived exosomes. Rafael da Fonseca Alves, Arnau Pallarès-Rusiñol, Rosanna Rossi, Merce Martí , Emilia Rezende Vaz, Thaise Gonçalves de Araújo, Maria Del Pilar Taboada Sotomayor and Maria Isabel Pividori. Biosensors and Bioelectronics 255, 2024, 116211. https://doi.org/10.1016/j.bios.2024.116211
Los exosomas. Nuevas herramientas para el diagnóstico de enfermedades no transmisibles en biopsias líquidas. Rosanna Rossi, Arnau Pallarès-Rusiñol, Mercé Martí, María Isabel Pividori. Actualidad Analítica 85, 2024, 15-20. ISSN 2444-8818. Sociedad española de química analítica.
2023
Magnetic Separation of Cell-Secreted Vesicles with Tailored Magnetic Particles and Downstream Applications. Bernuz, M., Pallarès-Rusiñol, A., Rossi, R., Fernández-Senac, C., Martí, M., Pividori, M.I. (2023). In: Vainio, S. (eds) Cell-Secreted Vesicles. ‘Methods in Molecular Biology’, vol 2668. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3203-1_18
Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment. Amanda Cano, Pablo García, Mireia Bernuz, Raquel Puerta, Itziar de Rojas, Ester Esteban-De Antonio, Alba Pérez-Cordón, Laura Montreal, Raúl Núñez, Óscar Sotolongo-Grau, Silvia Alonso-Lana, Emilio Alarcón-Martín, Sergi Valero, Montserrat Alegret, Joan Martínez, Elvira Martín, Miren Ettcheto, Assumpta Vivas, Marta Gomez-Chiari, Miguel Ángel Tejero, Adelina Orellana, Lluís Tárraga, Marta Marquié, Mercè Martí, María Isabel Pividori, Mercè Boada, Agustín Ruiz, Journal of Nanobiotechnology 2023, 21 (1), 1-19. https://doi.org/10.1186/s12951-023-01793-7
Electrochemical genosensing of overexpressed GAPDH transcripts in breast cancer exosomes. A Pallarès Rusiñol, Lima de Moura, M Martí, MI Pividori. Electrochemical genosensing of overexpressed GAPDH transcripts in breast cancer exosomes. Analytical chemistry, 2023, 95, 2487–2495 https://doi.org/10.1021/acs.analchem.2c04773.
Experimental data of the manuscript “Electrochemical Genosensing of Overexpressed GAPDH Transcripts in Breast Cancer Exosomes”. A Pallarès Rusiñol, Lima de Moura, M Martí, MI Pividori. Electrochemical genosensing of overexpressed GAPDH transcripts in breast cancer exosomes. 2023 | Data set. DOI: 10.34810/DATA681.
Advances in exosome analysis. A Pallares-Rusiñol, M Bernuz, S L Moura, C Fernández-Senac, R Rossi, M Martí and MI Pividori, in Advances in Clinical Chemistry 2023,112:69-117 https://doi.org/10.1016/bs.acc.2022.09.002
Extracellular vesicles, the emerging mirrors of brain physiopathology. Cano A, Ettcheto M, Bernuz M, Puerta R, Esteban de Antonio E, Sánchez-López E, Souto EB, Camins A, Martí M, Pividori MI, Boada M, Ruiz A. International Journal of Biological Sciences 19(3):721-743. doi:10.7150/ijbs.79063