Advancing Neurological Liquid Biopsy via Six-Base Sequencing of Cerebrospinal Fluid Cell-Free DNA

Starvaggi Cucuzza, C.; Rao Prakash, C.; Nolan, C.; Sepehri, M. H.; Simeone, A.; Sarre, L.; Charlesworth, T.; Puddu, F.; Han, Y.; Khademi, M.; Danylaite Karrenbauer, V.; Evertsson, B.; Fink, K.; Svenningsson, P.; Ingre, C.; Seitz, C.; Fang, F.; Constantinescu, R.; Novakova, L.; Thelin, E. P.; Piehl, F.; Kular, L.; Needhamsen, M.; Jagodic, M.

doi:10.64898/2026.09.06.749692

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bioRxiv · 10.64898/2026.09.06.749692

Advancing Neurological Liquid Biopsy via Six-Base Sequencing of Cerebrospinal Fluid Cell-Free DNA

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Abstract

Real-time molecular insights into the human brain are crucial for understanding neurological conditions and development of soluble biomarkers but challenged by the limited access to target tissue. Here we utilize 6-base sequencing to profile DNA modifications of cell-free DNA released from neural cells into cerebrospinal fluid. This strategy provides molecular, quantitative and qualitative insights into the ongoing neurodegenerative biology, which paves the way for liquid biopsy approaches to study neurological conditions.

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Starvaggi Cucuzza, C., Rao Prakash, C., Nolan, C., Sepehri, M. H., Simeone, A., Sarre, L., Charlesworth, T., Puddu, F., Han, Y., Khademi, M., Danylaite Karrenbauer, V., Evertsson, B., Fink, K., Svenningsson, P., Ingre, C., Seitz, C., Fang, F., Constantinescu, R., Novakova, L., Thelin, E. P., Piehl, F., Kular, L., Needhamsen, M., Jagodic, M.. 2026-09-13. Advancing Neurological Liquid Biopsy via Six-Base Sequencing of Cerebrospinal Fluid Cell-Free DNA. https://doi.org/10.64898/2026.09.06.749692

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