Other
20 Authors
- Huang Y,
- Zhang B,
- Zhang J,
- Wahane S,
- Li Y,
- Junqueira Alves C,
- Friedel RH,
- Zou H,
- Buxbaum JD,
- Crary JF,
- Wang M,
- Ni H,
- Kostic A,
- Hu B,
- Li A,
- Ho L,
- Neff R,
- Rios de Anda M,
- Brennand KJ,
- Kang S
| First Author | Huang Y | Year | 2024 |
| Journal | Nat Neurosci | Volume | 27 |
| Issue | 8 | Pages | 1489-1504 |
| PubMed ID | 38802590 | Mgi Jnum | J:363158 |
| Mgi Id | MGI:8159123 | Doi | 10.1038/s41593-024-01664-w |
| Citation | Huang Y, et al. (2024) Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer's disease. Nat Neurosci 27(8):1489-1504 |
| abstractText | Communication between glial cells has a profound impact on the pathophysiology of Alzheimer's disease (AD). We reveal here that reactive astrocytes control cell distancing in peri-plaque glial nets, which restricts microglial access to amyloid deposits. This process is governed by guidance receptor Plexin-B1 (PLXNB1), a network hub gene in individuals with late-onset AD that is upregulated in plaque-associated astrocytes. Plexin-B1 deletion in a mouse AD model led to reduced number of reactive astrocytes and microglia in peri-plaque glial nets, but higher coverage of plaques by glial processes, along with transcriptional changes signifying reduced neuroinflammation. Additionally, a reduced footprint of glial nets was associated with overall lower plaque burden, a shift toward dense-core-type plaques and reduced neuritic dystrophy. Altogether, our study demonstrates that Plexin-B1 regulates peri-plaque glial net activation in AD. Relaxing glial spacing by targeting guidance receptors may present an alternative strategy to increase plaque compaction and reduce neuroinflammation in AD. |
