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Age moderates the effects of traumatic brain injury on beta-amyloid plaque load in APP/PS1 mice
journal contributionposted on 2023-05-20, 03:46 authored by Jessica CollinsJessica Collins, Anna KingAnna King, Adele WoodhouseAdele Woodhouse, Matthew KirkcaldieMatthew Kirkcaldie, James VickersJames Vickers
Traumatic brain injury (TBI) has been identified as a risk factor for Alzheimer's disease (AD). However, how such neural damage contributes to AD pathology remains unclear; specifically, the relationship between the timing of a TBI relative to ageing and the onset of AD pathology is not known. In this study, we have examined the effect of TBI on subsequent beta-amyloid (Aβ) deposition in APP/PS1 (APPSWE/PSEN1dE9) transgenic mice either before (3 months of age) or after the onset (6 months of age) of plaque pathology. Lateral fluid percussion (LFPI), a model of diffuse brain injury, was induced in APP/PS1 and C57Bl/6 wild-type littermates (WT). LFPI caused a significant increase in both total (p<0.001) and fibrillar (p<0.001) Aβ plaque load in the cortex of 3-month-old APP/PS1 mice compared to sham treated mice at 30 days post-injury. However, in the cortex of 6-month-old mice at 30 days post-injury, LFPI caused a significant decrease in total (p<0.01), but not fibrillar (p>0.05), Aβ plaque load compared to sham treated mice. No Aβ plaques were present in any WT mice across these conditions. GFAP-immunolabelling of astrocytes and Iba-1-immunolabelling of microglial/macrophages was not significantly different (p<0.05) in injured animals compared to sham mice, or APP/PS1 mice compared to WT mice. The current data indicates that TBI may have differential effects on Aβ plaque deposition depending on age and the stage of amyloidosis at the time of injury.
J.O. & J.R. Wicking Trust
Publication titleJournal of Neurotrauma
Department/SchoolWicking Dementia Research Education Centre
PublisherMary Ann Liebert Inc Publ
Place of publication2 Madison Avenue, Larchmont, USA, Ny, 10538
Rights statementCopyright 2019 Mary Ann Liebert, Inc.