The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer's disease

Ameen-Ali, K. E. , Simpson, J. E., Wharton, S. B., Heath, P. R., Sharp, P. S., Brezzo, G. and Berwick, J. (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. (doi: 10.3233/JAD-181238) (PMID:30814360)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ameen-Ali, Dr Kamar
• Authors: Ameen-Ali, K. E., Simpson, J. E., Wharton, S. B., Heath, P. R., Sharp, P. S., Brezzo, G., and Berwick, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Alzheimer's Disease
• Publisher: IOS Press
• ISSN: 1387-2877
• ISSN (Online): 1875-8908
• Published Online: 29 March 2019
• Copyright Holders: Copyright © 2019 IOS Press
• First Published: First published in Journal of Alzheimer's Disease 68(2): 609-624
• Publisher Policy: Reproduced in accordance with the publisher copyright policy