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Early Regional Microglial Remodelling in the Hippocampus of the App NL‐G‐F Alzheimer's Model
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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...
| Published in: | Neuropathology and Applied Neurobiology |
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| ISSN: | 0305-1846 1365-2990 |
| Published: |
Wiley
2026
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa72158 |
| 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 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. |
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| Keywords: |
Alzheimer's disease, App NL-G-F, hippocampus, microglia, microglia morphology |
| College: |
Faculty of Science and Engineering |
| Funders: |
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. |
| Issue: |
3 |
| Start Page: |
e70082 |