| First Author | Sanford SAI | Year | 2024 |
| Journal | Alzheimers Dement | Volume | 20 |
| Issue | 2 | Pages | 1013-1025 |
| PubMed ID | 37849026 | Mgi Jnum | J:350211 |
| Mgi Id | MGI:7661199 | Doi | 10.1002/alz.13493 |
| Citation | Sanford SAI, et al. (2024) The type-I interferon response potentiates seeded tau aggregation and exacerbates tau pathology. Alzheimers Dement 20(2):1013-1025 |
| abstractText | INTRODUCTION: Signatures of a type-I interferon (IFN-I) response are observed in the post mortem brain in Alzheimer's disease (AD) and other tauopathies. However, the effect of the IFN-I response on pathological tau accumulation remains unclear. METHODS: We examined the effects of IFN-I signaling in primary neural culture models of seeded tau aggregation and P301S-tau transgenic mouse models in the context of genetic deletion of the IFN-I receptor (IFNAR). RESULTS: Polyinosinic:polycytidylic acid (PolyI:C), a synthetic analog of viral nucleic acids, evoked a potent cytokine response that enhanced seeded aggregation of tau in an IFN-I-dependent manner. IFN-I-induced vulnerability could be pharmacologically prevented and was intrinsic to neurons. Aged P301S-tau mice lacking Ifnar1 had significantly reduced tau pathology compared to mice with intact IFN signaling. DISCUSSION: We identify a critical role for IFN-I in potentiating tau aggregation. IFN-I is therefore identified as a potential therapeutic target in AD and other tauopathies. HIGHLIGHTS: Type-I IFN (IFN-I) promotes seeded tau aggregation in neural cultures. IFNAR inhibition prevents IFN-I driven sensitivity to tau aggregation. IFN-I driven vulnerability is intrinsic to neurons. Tau pathology is significantly reduced in aged P301S-tau mice lacking IFNAR. |
