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Peripheral treatment with enoxaparin exacerbates amyloid plaque pathology in Tg2576 mice

Citation

Cui, H and King, AE and Jacobson, GA and Small, DH, Peripheral treatment with enoxaparin exacerbates amyloid plaque pathology in Tg2576 mice, Journal of Neuroscience Research, 95, (4) pp. 992-999. ISSN 0360-4012 (2017) [Refereed Article]

Copyright Statement

Copyright 2016 Wiley Periodicals, Inc.

DOI: doi:10.1002/jnr.23880

Abstract

Alzheimer's disease (AD) is a complex, progressive neurological disorder characterized by the formation of extracellular amyloid plaques composed of β-amyloid protein (Aβ), the key component in pathogenesis of AD. Peripheral administration of enoxaparin (ENO) reportedly reduces the level of Aβ and the amyloid plaques in the cortex of amyloid precursor protein (APP) transgenic mice. However, the exact mechanism of these effects is unclear. Our previous studies indicated that ENO can inhibit APP processing to Aβ in primary cortical cells from Tg2576 mice by downregulating BACE1 levels. This study examines whether ENO-induced reduction of amyloid load is due to the decreased APP processing to Aβ in Tg2576 mice. Surprisingly, our results indicated that ENO significantly increases the Aβ42/Aβ40 ratio in cortex and enhances the amyloid plaque load in both cortex and hippocampus, although overall APP processing was not influenced by ENO. Moreover, ENO stimulated the aggregation of both Aβ40 and Aβ42 in vitro. Although ENO has been reported to improve cognition in vivo and has potential as a therapeutic agent for AD, the results from our study suggest that ENO can exacerbate the amyloid pathology, and the strategy of using ENO for the treatment of AD may require further assessment.

Item Details

Item Type:Refereed Article
Keywords:Alzheimer's disease, Aβ, amyloid plaques, amyloid precursor protein transgenic mice, enoxaparin, β-amyloid
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Cui, H (Mr Hao Cui)
Author:King, AE (Associate Professor Anna King)
Author:Jacobson, GA (Dr Glenn Jacobson)
Author:Small, DH (Professor David Small)
ID Code:110964
Year Published:2017 (online first 2016)
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-08-24
Last Modified:2017-11-06
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