Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology

Zoeb Jiwaji, Sachin S. Tiwari, Rolando X. Avilés-Reyes, Monique Hooley, David Hampton, Megan Torvell, Delinda A. Johnson, Jamie McQueen, Paul Baxter, Kayalvizhi Sabari-Sankar, Jing Qiu, Xin He, Jill Fowler, James Febery, Jenna Gregory, Jamie Rose, Jane Tulloch, Jamie Loan, David Story, Karina McDade, Amy M. Smith, Peta Greer, Matthew Ball, Peter C. Kind, Paul M. Matthews, Colin Smith, Owen Dando, Tara L. Spires-Jones, Jeffrey A. Johnson (), Siddharthan Chandran () and Giles E. Hardingham ()
Additional contact information
Zoeb Jiwaji: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Sachin S. Tiwari: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Rolando X. Avilés-Reyes: University of Wisconsin-Madison
Monique Hooley: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
David Hampton: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Megan Torvell: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Delinda A. Johnson: University of Wisconsin-Madison
Jamie McQueen: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Paul Baxter: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Kayalvizhi Sabari-Sankar: University of Wisconsin-Madison
Jing Qiu: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Xin He: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Jill Fowler: University of Edinburgh, Hugh Robson Building, George Square
James Febery: University of Edinburgh, Hugh Robson Building, George Square
Jenna Gregory: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Jamie Rose: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Jane Tulloch: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Jamie Loan: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
David Story: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Karina McDade: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Amy M. Smith: Burlington Danes Building, Hammersmith Hospital
Peta Greer: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Matthew Ball: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Peter C. Kind: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Paul M. Matthews: Burlington Danes Building, Hammersmith Hospital
Colin Smith: University of Edinburgh Chancellor’s Building
Owen Dando: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Tara L. Spires-Jones: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Jeffrey A. Johnson: University of Wisconsin-Madison
Siddharthan Chandran: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School
Giles E. Hardingham: UK Dementia Research Institute at the University of Edinburgh, Chancellor’s Building, Edinburgh Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-23

Abstract: Abstract Alzheimer’s disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis of astrocytes in APP/PS1 ß-amyloidopathy and MAPTP301S tauopathy mice revealed that only Aß influenced expression of AD risk genes, but both pathologies precociously induced age-dependent changes, and had distinct but overlapping signatures found in human post-mortem AD astrocytes. Both Aß and Tau pathology induced an astrocyte signature involving repression of bioenergetic and translation machinery, and induction of inflammation pathways plus protein degradation/proteostasis genes, the latter enriched in targets of inflammatory mediator Spi1 and stress-activated cytoprotective Nrf2. Astrocyte-specific Nrf2 expression induced a reactive phenotype which recapitulated elements of this proteostasis signature, reduced Aß deposition and phospho-tau accumulation in their respective models, and rescued brain-wide transcriptional deregulation, cellular pathology, neurodegeneration and behavioural/cognitive deficits. Thus, Aß and Tau induce overlapping astrocyte profiles associated with both deleterious and adaptive-protective signals, the latter of which can slow patho-progression.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27702-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27702-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27702-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().