Preprint Article Version 1 This version is not peer-reviewed

From Organotypic Mouse Brain Slices to Human Alzheimer’s Plasma Biomarkers: A Focus on Nerve Fiber Outgrowth

Version 1 : Received: 27 September 2024 / Approved: 27 September 2024 / Online: 30 September 2024 (13:07:23 CEST)

How to cite: YILMAZ, S. N.; Steiner, K.; Marksteiner, J.; Faserl, K.; Villunger, M.; Sarg, B.; Humpel, C. From Organotypic Mouse Brain Slices to Human Alzheimer’s Plasma Biomarkers: A Focus on Nerve Fiber Outgrowth. Preprints 2024, 2024092264. https://doi.org/10.20944/preprints202409.2264.v1 YILMAZ, S. N.; Steiner, K.; Marksteiner, J.; Faserl, K.; Villunger, M.; Sarg, B.; Humpel, C. From Organotypic Mouse Brain Slices to Human Alzheimer’s Plasma Biomarkers: A Focus on Nerve Fiber Outgrowth. Preprints 2024, 2024092264. https://doi.org/10.20944/preprints202409.2264.v1

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and progressive deterioration of cognitive functions. Being able to identify reliable biomarkers in easily available body fluids such as blood plasma is vital for the disease. To achieve this, we used a technique that applied human plasma to organotypic brain slice culture via microcontact print-ing. After a 2-week culture period, we performed immunolabeling for neurofilament and myelin oligodendrocyte glycoprotein (MOG) to visualize newly formed nerve fibers and oligodendro-cytes. There was no significant change in the number of new nerve fibers in the AD plasma group compared to the healthy control group, while the length of the produced fibers significantly de-creased. A significant increase in the number of MOG+ dots around these new fibers was detected in the patient group. According to our hypothesis, there are factors in the plasma of AD patients that affect the growth of new nerve fibers, which also affect the oligodendrocytes. Based on these findings, we selected the most promising plasma samples and conducted mass spectrometry us-ing a differential approach and we identified 3 putative biomarkers: aldehyde-dehydrogenase 1A1, alpha-synuclein and protein S100-A4. Our method represents a novel and innovative ap-proach to translate research findings from mouse models to human applications.

Keywords

Alzheimer’s disease; biomarker; plasma; organotypic brain slice; nerve fiber; myelin oligodendrocyte glycoprotein; microcontact printing; mass spectrometry

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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