Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model

Bevan, Ryan J.; Minett, Jessica; Smith, Alice L.; Figueras, Ana Cardus; Taylor, Philip R.

doi:10.1111/nan.70082

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Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model

Ryan J. Bevan

, Jessica Minett, Alice L. Smith, Ana Cardus Figueras

, Philip R. Taylor

Neuropathology and Applied Neurobiology, Volume: 52, Issue: 3, Start page: e70082

Swansea University Author: Jessica Minett

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© 2026 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. This is an open access article under the terms of the Creative Commons Attribution License.
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DOI (Published version): 10.1111/nan.70082

Abstract

Aims: Microglia undergo profound structural and functional changes during Alzheimer's disease, yet the earliest stages of morphological remodelling that occur prior to amyloid deposition remain poorly defined. We hypothesised that microglia in the hippocampus of App NL‐G‐F mice would exhibit ea...

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Published in:	Neuropathology and Applied Neurobiology
ISSN:	0305-1846 1365-2990
Published:	Wiley 2026
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa72158

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We hypothesised that microglia in the hippocampus of App NL‐G‐F mice would exhibit early, region‐specific structural adaptations before local plaque formation, reflecting an initial phase of disease‐associated structural remodelling. Methods: Two‐month‐old App NL‐G‐F and wildtype mice were examined using high‐resolution confocal microscopy of Iba1‐labelled microglia in the dorsal CA1 apical field. Automated three‐dimensional reconstructions were generated in Imaris, and quantitative morphometric analyses quantified cell density, Iba1 coverage, process topology and Sholl‐based arbor complexity. Statistical analyses were performed using linear mixed‐effects models incorporating sex as a fixed factor in all analyses. Results: Microglial density and total Iba1 coverage were unaffected in App NL‐G‐F mice at this age. In contrast, Sholl analysis revealed significant genotype‐dependent reductions in process intersections and total process length, accompanied by reduced individual‐cell territorial coverage, indicating an early contraction of the surveillance arbor independent of cell number. Conclusions: These findings demonstrate that hippocampal microglia in App NL‐G‐F mice undergo an early, coordinated structural remodelling before local amyloid deposition becomes apparent. 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spelling	2026-06-24T14:38:21.1646388 v2 72158 2026-06-24 Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model 8e592c5576ea17cb28d83f8dc45bd932 Jessica Minett Jessica Minett true false 2026-06-24 BGPS Aims: Microglia undergo profound structural and functional changes during Alzheimer's disease, yet the earliest stages of morphological remodelling that occur prior to amyloid deposition remain poorly defined. We hypothesised that microglia in the hippocampus of App NL‐G‐F mice would exhibit early, region‐specific structural adaptations before local plaque formation, reflecting an initial phase of disease‐associated structural remodelling. Methods: Two‐month‐old App NL‐G‐F and wildtype mice were examined using high‐resolution confocal microscopy of Iba1‐labelled microglia in the dorsal CA1 apical field. Automated three‐dimensional reconstructions were generated in Imaris, and quantitative morphometric analyses quantified cell density, Iba1 coverage, process topology and Sholl‐based arbor complexity. Statistical analyses were performed using linear mixed‐effects models incorporating sex as a fixed factor in all analyses. Results: Microglial density and total Iba1 coverage were unaffected in App NL‐G‐F mice at this age. In contrast, Sholl analysis revealed significant genotype‐dependent reductions in process intersections and total process length, accompanied by reduced individual‐cell territorial coverage, indicating an early contraction of the surveillance arbor independent of cell number. Conclusions: These findings demonstrate that hippocampal microglia in App NL‐G‐F mice undergo an early, coordinated structural remodelling before local amyloid deposition becomes apparent. This preplaque adaptation defines an early structural remodelling of hippocampal microglia prior to evident local amyloid deposition, providing new insight into the earliest structural adaptations associated with neuroimmune engagement in ad pathogenesis. Journal Article Neuropathology and Applied Neurobiology 52 3 e70082 Wiley 0305-1846 1365-2990 Alzheimer's disease, App NL-G-F, hippocampus, microglia, microglia morphology 1 6 2026 2026-06-01 10.1111/nan.70082 COLLEGE NANME Biosciences Geography and Physics School COLLEGE CODE BGPS Swansea University Another institution paid the OA fee This work is supported by the UK Dementia Research Institute (award number UK DRI-3203), which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. P.R.T is, in part, funded by the Moondance Foundation. 2026-06-24T14:38:21.1646388 2026-06-24T14:28:05.6245730 Faculty of Science and Engineering School of Biosciences, Geography and Physics - Biosciences Ryan J. Bevan 0000-0002-2557-2887 1 Jessica Minett 2 Alice L. Smith 3 Ana Cardus Figueras 0000-0003-4699-6205 4 Philip R. Taylor 0000-0003-0163-1421 5 72158__37043__52ab2f55a9b74e4784a0e680f49cf455.pdf nan.70082.pdf 2026-06-24T14:28:05.6063038 Output 14634955 application/pdf Version of Record true © 2026 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. This is an open access article under the terms of the Creative Commons Attribution License. true eng http://creativecommons.org/licenses/by/4.0/
title	Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model
spellingShingle	Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model Jessica Minett
title_short	Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model
title_full	Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model
title_fullStr	Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model
title_full_unstemmed	Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model
title_sort	Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model
author_id_str_mv	8e592c5576ea17cb28d83f8dc45bd932
author_id_fullname_str_mv	8e592c5576ea17cb28d83f8dc45bd932_***_Jessica Minett
author	Jessica Minett
author2	Ryan J. Bevan Jessica Minett Alice L. Smith Ana Cardus Figueras Philip R. Taylor
format	Journal article
container_title	Neuropathology and Applied Neurobiology
container_volume	52
container_issue	3
container_start_page	e70082
publishDate	2026
institution	Swansea University
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doi_str_mv	10.1111/nan.70082
publisher	Wiley
college_str	Faculty of Science and Engineering
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description	Aims: Microglia undergo profound structural and functional changes during Alzheimer's disease, yet the earliest stages of morphological remodelling that occur prior to amyloid deposition remain poorly defined. We hypothesised that microglia in the hippocampus of App NL‐G‐F mice would exhibit early, region‐specific structural adaptations before local plaque formation, reflecting an initial phase of disease‐associated structural remodelling. Methods: Two‐month‐old App NL‐G‐F and wildtype mice were examined using high‐resolution confocal microscopy of Iba1‐labelled microglia in the dorsal CA1 apical field. Automated three‐dimensional reconstructions were generated in Imaris, and quantitative morphometric analyses quantified cell density, Iba1 coverage, process topology and Sholl‐based arbor complexity. Statistical analyses were performed using linear mixed‐effects models incorporating sex as a fixed factor in all analyses. Results: Microglial density and total Iba1 coverage were unaffected in App NL‐G‐F mice at this age. In contrast, Sholl analysis revealed significant genotype‐dependent reductions in process intersections and total process length, accompanied by reduced individual‐cell territorial coverage, indicating an early contraction of the surveillance arbor independent of cell number. Conclusions: These findings demonstrate that hippocampal microglia in App NL‐G‐F mice undergo an early, coordinated structural remodelling before local amyloid deposition becomes apparent. This preplaque adaptation defines an early structural remodelling of hippocampal microglia prior to evident local amyloid deposition, providing new insight into the earliest structural adaptations associated with neuroimmune engagement in ad pathogenesis.
published_date	2026-06-01T06:14:05Z
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Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model

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