From Organotypic Mouse Brain Slices to Human Alzheimer Plasma Biomarkers: A Focus on Microglia

Autor: Katharina Steiner, Sakir Necat Yilmaz, Alessa Gern, Josef Marksteiner, Klaus Faserl, Mathias Villunger, Bettina Sarg, Christian Humpel
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Biomolecules, Vol 14, Iss 9, p 1109 (2024)
Druh dokumentu: article
ISSN: 2218-273X
DOI: 10.3390/biom14091109
Popis: Alzheimer’s disease is a severe neurodegenerative disorder, and the discovery of biomarkers is crucial for early diagnosis. While the analysis of biomarkers in cerebrospinal fluid is well accepted, there are currently no blood biomarkers available. Our research focuses on identifying novel plasma biomarkers for Alzheimer’s disease. To achieve this, we employed a technique that involves coupling human plasma to mouse organotypic brain slices via microcontact prints. After culturing for two weeks, we assessed Iba1-immunopositive microglia on these microcontact prints. We hypothesized that plasma from Alzheimer’s patients contains factors that affect microglial migration. Our data indicated that plasma from Alzheimer’s patients significantly inhibited the migration of round Iba1-immunoreactive microglia (13 ± 3, n = 24, p = 0.01) compared to healthy controls (50 ± 16, n = 23). Based on these findings, we selected the most promising plasma samples and conducted mass spectrometry using a differential approach, and we identified four potential biomarkers: mannose-binding protein C, macrophage receptor MARCO, complement factor H-related protein-3, and C-reactive protein. Our method represents a novel and innovative approach to translate research findings from mouse models to human applications.
Databáze: Directory of Open Access Journals
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