From Organotypic Mouse Brain Slices to Human Alzheimer Plasma Biomarkers: A Focus on Microglia
Abstract
:1. Introduction
1.1. Biomarkers in Alzheimer’s Disease
1.2. Plasma Biomarkers in Alzheimer’s Disease
1.3. Microglia in Alzheimer’s Disease
1.4. Organotypic Brain Slices as a Tool to Search for Biomarkers
2. Materials and Methods
2.1. Human Plasma Samples
2.2. Microcontact Printing of Human Plasma
2.3. Organotypic Brain Slices
2.4. Immunofluorescence for Microglia
2.5. Mass Spectrometry
2.6. Data Analysis and Statistics
3. Results
3.1. Efficiency of Plasma Microcontact Printing
3.2. Iba1-Postive Microglial Immunoreactivity
3.3. Effects of MCP-1 on Microglial Migration
3.4. Epidemiology of the Patients in This Study
3.5. Effects of Plasma on Migration of Iba1-Positive Microglia
3.6. Mass Spectrometry
4. Discussion
4.1. Iba1-Positive Microglia in Organotypic Brain Slices
4.2. Microcontact Printing for Delivering Plasma to Brain Slices
4.3. Effects of Microcontact-Printed MCP-1 on Microglia
4.4. Effects of Microcontact-Printed Plasma on Microglia
4.5. Differential Mass Spectrometry
4.6. Limitations of the Study
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Treatment | n | Round | Ramified | Macrophagic | Length |
---|---|---|---|---|---|
Minus medium | 5 | 0.2 ± 0.2 vs. | 0.2 ± 0.2 vs. | 0.8 ± 0.2 vs. | 255 ± 89 vs. |
MCP-1 medium | 7 | 2.7 ± 1.7 ** | 6.7 ± 3.6 ** | 3.0 ± 0.7 ** | 364 ± 96 |
µCP (-) | 5 | 5.8 ± 2.3 vs. | 8.4 ± 3.3 vs. | 7.0 ± 2.4 vs. | 591 ± 76 vs. |
µCP (MCP-1) | 10 | 4.8 ± 1.7 | 28.2 ± 6.1 *** | 14.0 ± 3.2 * | 864 ± 26 |
µCP (Plasma) | 6 | 13.1 ± 5.5 vs. | 16.0 ± 5.9 vs. | 16.0 ± 7.9 vs. | 721 ± 63 vs. |
µCP (Plasma+MCP-1) | 10 | 11.3 ± 3.2 | 31.6 ± 6.2 ** | 9.4 ± 1.8 | 861 ± 63 |
Patient | n | Male | Age | MMSE | GDS |
---|---|---|---|---|---|
Control | 23 | 13 | 73 ± 1.5 vs. | 29.6 ± 0.1 vs. | 3.8 ± 0.5 vs. |
MCI | 25 | 9 | 75 ± 1.6 | 27.4 ± 0.2 * | 4.4 ± 0.6 |
AD | 24 | 4 | 81 ± 1.5 ** | 18.9 ± 1.2 *** | 5.0 ± 0.6 |
Group | n | Round | Ramified | Macrophagic | Length |
---|---|---|---|---|---|
Control | 23 | 49.6 ± 16 vs. | 12.5 ± 1.9 vs. | 12.5 ± 2.6 vs. | 400 ± 50 vs. |
MCI | 25 | 27.1 ± 6 | 11.1 ± 2.6 | 10.5 ± 2.2 | 441 ± 51 |
AD | 24 | 12.9 ± 3 p = 0.01 * | 10.0 ± 2.2 | 13.1 ± 3.0 | 424 ± 55 |
Putative Biomarker Identified | Symbol | Acc. No. | MW (kDa) | # Unique Peptides | Change in AD | Identity (%) | Similarity (%) |
---|---|---|---|---|---|---|---|
Mannose-binding protein C | MBL2 | P11226 | 26.1 | 10 | 5.5 ↑ | 60.2 | 75.2 |
Macrophage receptor MARCO | MARCO | Q9UEW3 | 52.6 | 4 | 0.5 ↓ | 66.9 | 77.1 |
Complement factor H-related protein-3 | CFHR3 | Q02985 | 37.3 | 3 | 0.5 ↓ | 45.4 | 59.3 |
C-reactive protein | CRP | P02741 | 25 | 6 | 0.3 ↓ | 70.1 | 83 |
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Steiner, K.; Yilmaz, S.N.; Gern, A.; Marksteiner, J.; Faserl, K.; Villunger, M.; Sarg, B.; Humpel, C. From Organotypic Mouse Brain Slices to Human Alzheimer Plasma Biomarkers: A Focus on Microglia. Biomolecules 2024, 14, 1109. https://doi.org/10.3390/biom14091109
Steiner K, Yilmaz SN, Gern A, Marksteiner J, Faserl K, Villunger M, Sarg B, Humpel C. From Organotypic Mouse Brain Slices to Human Alzheimer Plasma Biomarkers: A Focus on Microglia. Biomolecules. 2024; 14(9):1109. https://doi.org/10.3390/biom14091109
Chicago/Turabian StyleSteiner, Katharina, Sakir Necat Yilmaz, Alessa Gern, Josef Marksteiner, Klaus Faserl, Mathias Villunger, Bettina Sarg, and Christian Humpel. 2024. "From Organotypic Mouse Brain Slices to Human Alzheimer Plasma Biomarkers: A Focus on Microglia" Biomolecules 14, no. 9: 1109. https://doi.org/10.3390/biom14091109