| First Author | Seo DO | Year | 2023 |
| Journal | Science | Volume | 379 |
| Issue | 6628 | Pages | eadd1236 |
| PubMed ID | 36634180 | Mgi Jnum | J:343013 |
| Mgi Id | MGI:7428832 | Doi | 10.1126/science.add1236 |
| Citation | Seo DO, et al. (2023) ApoE isoform- and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy. Science 379(6628):eadd1236 |
| abstractText | Tau-mediated neurodegeneration is a hallmark of Alzheimer's disease. Primary tauopathies are characterized by pathological tau accumulation and neuronal and synaptic loss. Apolipoprotein E (ApoE)-mediated neuroinflammation is involved in the progression of tau-mediated neurodegeneration, and emerging evidence suggests that the gut microbiota regulates neuroinflammation in an APOE genotype-dependent manner. However, evidence of a causal link between the microbiota and tau-mediated neurodegeneration is lacking. In this study, we characterized a genetically engineered mouse model of tauopathy expressing human ApoE isoforms reared under germ-free conditions or after perturbation of their gut microbiota with antibiotics. Both of these manipulations reduced gliosis, tau pathology, and neurodegeneration in a sex- and ApoE isoform-dependent manner. The findings reveal mechanistic and translationally relevant interrelationships between the microbiota, neuroinflammation, and tau-mediated neurodegeneration. |
