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Network analysis identifies strain-dependent response to tau and tau seeding-associated genes.

Authors :
Acri DJ
You Y
Tate MD
Karahan H
Martinez P
McCord B
Sharify AD
John S
Kim B
Dabin LC
Philtjens S
Wijeratne HRS
McCray TJ
Smith DC
Bissel SJ
Lamb BT
Lasagna-Reeves CA
Kim J
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