| First Author | Foley KE | Year | 2025 |
| Journal | J Neurosci | Volume | 45 |
| Issue | 5 | PubMed ID | 39741000 |
| Mgi Jnum | J:361442 | Mgi Id | MGI:7858829 |
| Doi | 10.1523/JNEUROSCI.1456-24.2024 | Citation | Foley KE, et al. (2025) Acute Communication Between Microglia and Nonparenchymal Immune Cells in the Anti-Abeta Antibody-Injected Cortex. J Neurosci 45(5) |
| abstractText | Anti-Abeta immunotherapy use to treat Alzheimer's disease is on the rise. While anti-Abeta antibodies provide hope in targeting Abeta plaques in the brain, there still remains a lack of understanding regarding the cellular responses to these antibodies in the brain. In this study, we sought to identify the acute effects of anti-Abeta antibodies on immune responses. To determine cellular changes due to anti-Abeta antibody exposure, we intracranially injected 14 mo APP male and female mice with anti-Abeta IgG1 (6E10) or control IgG1 into the cortex. After 24 h or 3 d, we harvested the cortex and performed a glial cell-enriched preparation for single-cell sequencing. Cell types, proportions, and cell-to-cell signaling were evaluated between the two injection conditions and two acute timepoints. We identified 23 unique cell clusters including microglia, astrocytes, endothelial cells, neurons, oligos/OPCs, immune cells, and unknown. The anti-Abeta antibody-injected cortices revealed more ligand-receptor (L-R) communications between cell types, as well as stronger communications at only 24 h. At 3 d, while there were more L-R communications for the anti-Abeta antibody condition, the strength of these connections was stronger in the control IgG condition. We also found evidence of an initial and strong communication emphasis in microglia-to-nonparenchymal immune cells at 24 h, specifically in the TGFbeta signaling pathway. We identify several pathways that are specific to anti-Abeta antibody exposure at acute timepoints. These data lay the groundwork for understanding the brain's unique response to anti-Abeta antibodies. |
