Transgenic A53T Mice Have Astrocytic α-Synuclein Aggregates in Dopamine and Striatal Regions.
Overview
- Charles Perkins Centre & Faculty of Medicine and Health School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia
- Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA
- Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia
- Neuroscience Research Australia, Sydney, New South Wales, Australia
- NysnoBio, Mills Valley, California, USA
- The Florey Institute of Neuroscience and Mental Health & The University of Melbourne, Parkville, Victoria, Australia
- BRAINS Unit, BMC D11, Lund University, Lund, Sweden
- Brain and Mind Centre & Faculty of Medicine and Health School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia
Abstract
Aims: The accumulation of α‐synuclein in astrocytes in Parkinson's disease is considered to be secondary to neuronal accumulation. The aim of this study to identify whether astrocytes accumulate small α‐synuclein aggregates before or after neurons in the nigrostriatal pathway.
Methods: Fixed serial midbrain and striatal sections from M83 A53T transgenic mouse model of Parkinson's disease and wild‐type controls were histologically processed for multiplex labelling of α‐synuclein and astrocytic markers and astrocyte quantitation performed on digital images using QuPath software.
Results: The density of astrocytes within the substantia nigra pars compacta was approximately 30% greater compared with other sampled regions (p < 0.005). Small aggregates of α‐synuclein were observed in astrocytic processes, including in wild‐type mice where a quarter of all astrocytes had an obvious α‐synuclein aggregate. Compared to wild‐type, A53T transgenic astrocytes had significantly enlarged somas (p < 0.001) with more processes (p < 0.001) consistent with a reactive phenotype. The A53T transgenic mice had more than double the numbers of astrocytes (p < 0.001) and 2.5 times more astrocytes with α‐synuclein aggregates compared to wild‐type mice (p < 0.001).
Conclusions: These data suggest that small α‐synuclein aggregates are normally cleared by astrocytes and that the substantia nigra pars compacta requires more astrocytic support for this function than other midbrain dopaminergic regions or the striatum. This adds another vulnerability factor to those already known for the substantia nigra with early deficits in clearance of small α‐synuclein aggregates by astrocytes associated with increased astrocytic reactivity in the A53T transgenic mouse model.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- biostudies:S-BIAD2485 — at BioStudies; found in “Data Availability Statement”
- zenodo:18345432 — at Zenodo; found in “Data Availability Statement”
Data Availability Statement
The data, code, protocols and key lab materials used and generated in this study are listed in a Key Resource Table alongside their persistent identifiers at Zenodo https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 3, 28 September 2026
- Publisher: — → Wiley
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 10 MeSH terms, 2 funders, 58 references, 14 RRIDs.
Cite
This paper
Peat, C., Prasad, A., Finkelstein, D. I., Sue, C., Johnston, J. A., Parish, C. L., Thompson, L., Kirik, D., & Halliday, G. M. (2026). Transgenic A53T Mice Have Astrocytic α-Synuclein Aggregates in Dopamine and Striatal Regions. Neuropathology and applied neurobiology, 52(4), e70097. https://
BibTeX
@article{peat2026transge
author = {Peat, Cormac and Prasad, Asheeta and Finkelstein, David I and Sue, Caroline and Johnston, Jennifer A and Parish, Clare L and Thompson, Lachlan and Kirik, Deniz and Halliday, Glenda M},
title = {{Transgenic A53T Mice Have Astrocytic α-Synuclein Aggregates in Dopamine and Striatal Regions}},
journal = {Neuropathology and applied neurobiology},
year = {2026},
month = aug,
volume = {52},
number = {4},
pages = {e70097},
publisher = {Wiley},
issn = {0305-1846},
doi = {10.1111/
url = {https://
pmid = {42608961},
pmcid = {PMC13482139}
}
RIS
TY - JOUR
AU - Peat, Cormac
AU - Prasad, Asheeta
AU - Finkelstein, David I
AU - Sue, Caroline
AU - Johnston, Jennifer A
AU - Parish, Clare L
AU - Thompson, Lachlan
AU - Kirik, Deniz
AU - Halliday, Glenda M
TI - Transgenic A53T Mice Have Astrocytic α-Synuclein Aggregates in Dopamine and Striatal Regions
T2 - Neuropathology and applied neurobiology
J2 - Neuropathol Appl Neurobiol
PY - 2026
DA - 2026/
VL - 52
IS - 4
SP - e70097
SN - 0305-1846
PB - Wiley
DO - 10.1111/
UR - https://
LA - en
ER -
CSL-JSON
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