Other
19 Authors
- Fan L,
- Gan L,
- Condello C,
- Khawaja RR,
- Grinberg LT,
- Luo W,
- Cuervo AM,
- Le D,
- Miller BL,
- Liu B,
- Zhou Y,
- Chin M,
- Wang C,
- Li Y,
- Seeley WW,
- Zhan L,
- Gestwicki JE,
- Mok SA,
- Kodama L
| First Author | Wang C | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 1969 |
| PubMed ID | 35413950 | Mgi Jnum | J:355365 |
| Mgi Id | MGI:7265955 | Doi | 10.1038/s41467-022-29552-6 |
| Citation | Wang C, et al. (2022) Microglial NF-kappaB drives tau spreading and toxicity in a mouse model of tauopathy. Nat Commun 13(1):1969 |
| abstractText | Activation of microglia is a prominent pathological feature in tauopathies, including Alzheimer's disease. How microglia activation contributes to tau toxicity remains largely unknown. Here we show that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling, activated by tau, drives microglial-mediated tau propagation and toxicity. Constitutive activation of microglial NF-kappaB exacerbated, while inactivation diminished, tau seeding and spreading in young PS19 mice. Inhibition of NF-kappaB activation enhanced the retention while reduced the release of internalized pathogenic tau fibrils from primary microglia and rescued microglial autophagy deficits. Inhibition of microglial NF-kappaB in aged PS19 mice rescued tau-mediated learning and memory deficits, restored overall transcriptomic changes while increasing neuronal tau inclusions. Single cell RNA-seq revealed that tau-associated disease states in microglia were diminished by NF-kappaB inactivation and further transformed by constitutive NF-kappaB activation. Our study establishes a role for microglial NF-kappaB signaling in mediating tau spreading and toxicity in tauopathy. |
