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Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease.

Overview

Authors: Michelle L Munro1,2, Ruben Vergara Silva1,2,3, Shane M Ohline1,2,3, Ei Phyo Khaing1,2, Joan A Chan1,2,3, Mohamed F Ibrahim1,3, Tausi F Tausi1,2, Wickliffe C Abraham3,4, Peter P Jones1,2,3
  1. Department of Physiology, Faculty of Biomedical Sciences, University of Otago, Dunedin, New Zealand
  2. HeartOtago, University of Otago, Dunedin, New Zealand
  3. Brain Health Research Centre, University of Otago, Dunedin, New Zealand
  4. Department of Psychology, University of Otago, Dunedin, New Zealand
Institutions: University of Otago (New Zealand)
Journal: Acta physiologica (Oxford, England), volume 242, issue 7, article e70264
Dates: received 20 March 2026; accepted 27 May 2026; published online 5 June 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1111/apha.70264 · PMID 42249616 · PMCID PMC13241622 · OpenAlex W7163734922
Open access: hybrid, a free copy (OpenAlex)
Status: dead link
Categories: mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Machine learning
Keywords: Alzheimer's disease, CA1 hippocampal neurons, calcium channels, dSTORM, RyR2, super‐resolution imaging
MeSH: Alzheimer Disease*, Neurons*, Ryanodine Receptor Calcium Release Channel*, Amyloid beta-Protein Precursor, Animals, Calcium, Calcium Signaling, Disease Models, Animal, Mice, Mice, Transgenic, Presenilin-1 (* major topic)
Topic: Ion channel regulation and function (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Health Research Council of New Zealand (20/625, 20/370); Marsden Fund (UOO2009); Neurological Foundation of New Zealand (2011 PGR)
Citations: not cited yet (Europe PMC); 47 references in the paper

Abstract

Aim: The ryanodine receptor (RyR2) is an intracellular Ca2+ release channel which mediates numerous cellular functions across different tissues. Dysregulation of RyR2 channel activity leads to pathological Ca2+ release, which often underlies disrupted cellular signaling in disease states. In the heart, RyR2 channels forms discrete clusters and calcium release units (CRUs) which control channel activity. These structures demonstrate nanoscale remodeling in disease states associated with pathological Ca2+ release activity in the heart. Hence, these nanoscale structures are critical in regulating Ca2+ release in health and disease. RyR2 is also expressed in brain; however, whether analogous clusters and CRUs form in neurons remains unexplored.

Methods: Using super‐resolution imaging, we assessed RyR2 organization in CA1 pyramidal neurons of wild‐type mice. Furthermore, we used the APP/PS1 mouse model of Alzheimer's disease (AD) to assess whether there is nanoscale remodeling of RyR2 in a setting associated with pathological Ca2+ release in neurons.

Results: Here, we provide the first identification and detailed characterization of RyR2 clusters in central nervous system neurons, which are comparable to those reported in the heart. Moreover, we observed a decrease in RyR2 cluster size and reduced CRU organization in AD mice at an age associated with high plaque burden and cognitive deficits. This remodeling is analogous to that reported in pathological states in the heart.

Conclusion: Together, these findings implicate the nanoscale remodeling of RyR2 clusters and CRUs as a novel mechanism underlying Ca2+ channel dysregulation and neuronal dysfunction in AD.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

david_baddeley/python-microscopy

License: none: the authors keep all their rights
State: the link is dead, verified on 27 September 2026
Evidence: found in the paper
Software Heritage: archived
Found in: the text, “Confocal and dSTORM Imaging”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link is dead
  • 27 September 2026: the link is dead

The paper's code and data availability statement is in the Data section.

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  • 0 scripts, each with its path and the digest of its content;
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Data

No dataset and no data link were found in the paper.

Data Availability Statement

All data underlying the study will be made openly available in the Github (github.com) repository.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Wiley

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 6 keywords, 11 MeSH terms, 3 funders, 47 references.

Cite

This paper

Munro, M. L., Silva, R. V., Ohline, S. M., Khaing, E. P., Chan, J. A., Ibrahim, M. F., Tausi, T. F., Abraham, W. C., & Jones, P. P. (2026). Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease. Acta physiologica (Oxford, England), 242(7), e70264. https://doi.org/10.1111/apha.70264

BibTeX

@article{munro2026clustering,
author = {Munro, Michelle L and Silva, Ruben Vergara and Ohline, Shane M and Khaing, Ei Phyo and Chan, Joan A and Ibrahim, Mohamed F and Tausi, Tausi F and Abraham, Wickliffe C and Jones, Peter P},
title = {{Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease}},
journal = {Acta physiologica (Oxford, England)},
year = {2026},
month = jul,
volume = {242},
number = {7},
pages = {e70264},
publisher = {Wiley},
issn = {1748-1708},
doi = {10.1111/apha.70264},
url = {https://doi.org/10.1111/apha.70264},
pmid = {42249616},
pmcid = {PMC13241622}
}

RIS

TY - JOUR
AU - Munro, Michelle L
AU - Silva, Ruben Vergara
AU - Ohline, Shane M
AU - Khaing, Ei Phyo
AU - Chan, Joan A
AU - Ibrahim, Mohamed F
AU - Tausi, Tausi F
AU - Abraham, Wickliffe C
AU - Jones, Peter P
TI - Clustering Properties of Neuronal Ryanodine Receptor 2 and Remodeling in the APP/PS1 Mouse Model of Alzheimer's Disease
T2 - Acta physiologica (Oxford, England)
J2 - Acta Physiol (Oxf)
PY - 2026
DA - 2026/07/01
VL - 242
IS - 7
SP - e70264
SN - 1748-1708
PB - Wiley
DO - 10.1111/apha.70264
UR - https://doi.org/10.1111/apha.70264
LA - en
ER -

CSL-JSON

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