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Network analysis identifies strain-dependent response to tau and tau seeding-associated genes.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2023 Nov 06; Vol. 220 (11). Date of Electronic Publication: 2023 Aug 22. - Publication Year :
- 2023
-
Abstract
- Previous research demonstrated that genetic heterogeneity is a critical factor in modeling amyloid accumulation and other Alzheimer's disease phenotypes. However, it is unknown what mechanisms underlie these effects of genetic background on modeling tau aggregate-driven pathogenicity. In this study, we induced tau aggregation in wild-derived mice by expressing MAPT. To investigate the effect of genetic background on the action of tau aggregates, we performed RNA sequencing with brains of C57BL/6J, CAST/EiJ, PWK/PhJ, and WSB/EiJ mice (n = 64) and determined core transcriptional signature conserved in all genetic backgrounds and signature unique to wild-derived backgrounds. By measuring tau seeding activity using the cortex, we identified 19 key genes associated with tau seeding and amyloid response. Interestingly, microglial pathways were strongly associated with tau seeding activity in CAST/EiJ and PWK/PhJ backgrounds. Collectively, our study demonstrates that mouse genetic context affects tau-mediated alteration of transcriptome and tau seeding. The gene modules associated with tau seeding provide an important resource to better model tauopathy.<br /> (© 2023 Acri et al.)
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 220
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 37606887
- Full Text :
- https://doi.org/10.1084/jem.20230180