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J Neurosci Res. 2017 Apr;95(4):992-999. doi: 10.1002/jnr.23880. Epub 2016 Aug 21.

Peripheral treatment with enoxaparin exacerbates amyloid plaque pathology in Tg2576 mice.

Author information

1
College of Life Science, Jiangxi Normal University, Nanchang, China.
2
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
3
School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
4
Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.

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.

KEYWORDS:

Alzheimer's disease; Aβ; amyloid plaques; amyloid precursor protein transgenic mice; enoxaparin; β-amyloid

PMID:
27546887
DOI:
10.1002/jnr.23880
[Indexed for MEDLINE]

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