Ameen-Ali, K., Simpson, J., Wharton, S. et al. (4 more authors) (2019) The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer’s disease. Journal of Alzheimer's Disease, 68 (2). pp. 609-624. ISSN 1387-2877
Abstract
The role of cellular changes in the neurovascular unit is increasingly being investigated to understand the pathogenesis of Alzheimer’s disease (AD). The aim of the current study was to determine the time course of recognition memory impairment in the J20 mouse model of AD, in relation to neuroinflammatory responses and the pathology of amyloid-β (Aβ). Male hAPP-J20 and wild-type mice were assessed at 3, 6, 9, and 12 months of age. The spontaneous object recognition (SOR) task provided a measure of memory, with assessment of both a short delay (1 min) and a long delay (4 h). Immunohistochemistry was used to characterize Aβ deposition, and quantify astrocyte and microglial responses. At all ages tested, J20 mice had impaired long-term, but preserved short-term, recognition memory. Wild-types demonstrated preserved long-term memory up to 9 months of age, and preserved short-term memory at all ages tested. Plaque pathology in the J20 mice was present from 6 months onwards, with co-localization of reactive microglia and activated astrocytes. Reactive microglia and astrocyte activation in the hippocampus were significantly greater in the J20 mice at 9 months, compared to wild-types. This study contributes to our understanding of the pathological and cognitive mechanisms at play in AD. J20 mice showed impairment in retaining information over longer periods from an early age, preceding the deposition of Aβ and glial activation. Defining early physiological changes in relation to cognitive decline could provide insight into new therapeutic targets early in the disease process, when intervention is most likely to effectively slow disease progression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 IOS Press. This is an author produced version of a paper subsequently published in Journal of Alzheimer's Disease. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Alzheimer’s disease; hAPP-J20; recognition memory; amyloid; astrocytes; microglia |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) |
Funding Information: | Funder Grant number ALZHEIMERS RESEARCH UK ARUK-IRG2014-10 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Jan 2019 15:31 |
Last Modified: | 16 Nov 2021 12:37 |
Status: | Published |
Publisher: | IOS Press |
Refereed: | Yes |
Identification Number: | 10.3233/JAD-181238 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:141625 |