{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sanford SAI"],"funding":["UK Dementia Research Institute","Medical Research Council","Alzheimer's Society","Wellcome Trust"],"pagination":["1013-1025"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10916982"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(2)"],"pubmed_abstract":["<h4>Introduction</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Highlights</h4>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."],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["The type-I interferon response potentiates seeded tau aggregation and exacerbates tau pathology."],"pmcid":["PMC10916982"],"funding_grant_id":["MC_U105181010","UKDRI-2010","488","206248/Z/17/Z","223054/Z/21/Z"],"pubmed_authors":["Sanford SAI","Syanda V","Vaysburd M","Clark J","James LC","McEwan WA","Tuck BJ","Miller LVC","Keeling S","Neumann M"],"additional_accession":[]},"is_claimable":false,"name":"The type-I interferon response potentiates seeded tau aggregation and exacerbates tau pathology.","description":"<h4>Introduction</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Highlights</h4>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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-04-20T02:52:09.072Z","creation":"2025-04-20T02:52:09.072Z"},"accession":"S-EPMC10916982","cross_references":{"pubmed":["37849026"],"doi":["10.1002/alz.13493"]}}