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bioRxiv · 10.1101/495960

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.·Brezzo, G.·Berwick, J.
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Abstract

The role of cellular changes in the neurovascular unit is increasingly being investigated to understand the pathogenesis of Alzheimers disease. 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 A{beta}.\n\nMale 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 hrs). Immunohistochemistry was used to characterise A{beta}-deposition, and quantify astrocyte and microglial responses.\n\nAt 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-localisation 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.\n\nThis 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 A{beta} 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.

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Ameen-Ali, K. E., Simpson, J. E., Wharton, S. B., Heath, P. R., Sharp, P., Brezzo, G., Berwick, J.. 2018-12-13. The Time Course of Recognition Memory Impairment and Glial Pathology in the hApp-J20 Mouse Model of Alzheimer’s Disease. https://doi.org/10.1101/495960

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