| First Author | Lu Y | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 7 | Pages | 112785 |
| PubMed ID | 37436901 | Mgi Jnum | J:338304 |
| Mgi Id | MGI:7511289 | Doi | 10.1016/j.celrep.2023.112785 |
| Citation | Lu Y, et al. (2023) Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer's disease model mice. Cell Rep 42(7):112785 |
| abstractText | Peripheral inflammation has been linked to various neurodegenerative disorders, including Alzheimer's disease (AD). Here we perform bulk, single-cell, and spatial transcriptomics in APP/PS1 mice intranasally exposed to Staphylococcus aureus to determine how low-grade peripheral infection affects brain transcriptomics and AD-like pathology. Chronic exposure led to increased amyloid plaque burden and plaque-associated microglia, significantly affecting the transcription of brain barrier-associated cells, which resulted in barrier leakage. We reveal cell-type- and spatial-specific transcriptional changes related to brain barrier function and neuroinflammation during the acute infection. Both acute and chronic exposure led to brain macrophage-associated responses and detrimental effects in neuronal transcriptomics. Finally, we identify unique transcriptional responses at the amyloid plaque niches following acute infection characterized by higher disease-associated microglia gene expression and a larger effect on astrocytic or macrophage-associated genes, which could facilitate amyloid and related pathologies. Our findings provide important insights into the mechanisms linking peripheral inflammation to AD pathology. |
