Novel Plasma Biomarkers for Alzheimer's Disease: Insights from Organotypic Brain Slice and Microcontact Printing Techniques.

Background: Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by beta-amyloid plaques and tau neurofibrillary tangles. The diagnosis of AD is complex, with the analysis of beta-amyloid and tau in cerebrospinal fluid being a well-established diagnostic approach. However, currently no blood biomarkers have been identified or validated for clinical use. In the present study, we will identify novel plasma biomarkers for AD using our well-established organotypic mouse brain slice model connected to microcontact prints. We hypothesize that AD plasma contains factors that affect endothelial cell migration and new vessel formation.

Methods: In the present study, plasma from human patients is microcontact printed and connected to mouse brain slices. After 4 weeks in culture, laminin⁺ and lectin⁺ endothelial cells (ECs) and vessels are analyzed by immunostaining techniques. The most promising samples were processed by differential mass spectrometry.

Results: Our data show that AD plasma significantly increased the migration length of laminin⁺ and lectin⁺ ECs along the microcontact prints. Using differential mass spectrometry, we could identify three potential biomarkers: C-reactive protein, basigin, and trem-like transcript 1 protein.

Conclusion: Here we show that brain slices connected to human plasma prints allow the identification of novel human AD biomarkers with subsequent mass spectrometry. This technique represents a novel and innovative approach to translate research findings from mouse models to human applications.