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In vivo uptake of β-amyloid by non-plaque associated microglia

Hawkes, Cheryl A.; Deng, LeHua; Fenili, Daniela; Nitz, Mark and McLaurin, JoAnne (2012). In vivo uptake of β-amyloid by non-plaque associated microglia. Current Alzheimer Research, 9(8) pp. 890–901.

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The role of microglia in β-amyloid (Aβ) deposition or clearance in the Alzheimer's disease (AD) brain remains unclear. Previous in vivo studies have focused primarily on the association of microglia with Aβ-positive parenchymal plaques, but have given little consideration to the possible interaction between Aβ and non-plaque associated microglia. Further, it is not known if microglia play a direct role in mediating Aβ uptake following anti-aggregant treatment. We report here the identification of Aβ-positive processes throughout the cortex and hippocampus of TgCRND8 mice expressing the human Swedish (KM670/671NL) and Indiana (V717F) amyloid precursor protein mutations, which localized to ionized calcium binding protein-1-positive resident microglia that were not associated with extracellular plaques. Oral administration of 1-deoxy-1-fluoro-scyllo-inositol, a scyllo-inositol analogue, to TgCRND8 mice improved spatial memory impairments and suppressed amyloid pathology in a dose-dependent manner. Further, treatment with 1-deoxy-1- fluoro-scyllo-inositol significantly increased hippocampal intra-microglial Aβ levels without stimulating microglial proliferation or peripheral macrophage recruitment. These results reveal a novel, beneficial role for non-plaque associated microglia in the regulation of cerebral Aβ levels in a mouse model of AD.

Item Type: Journal Item
Copyright Holders: 2012 Eureka Science Ltd.
ISSN: 1875-5828
Keywords: Alzheimer’s disease; anti-aggregant; transgenic mouse model; microglia; immunoblotting; central nervous system; β-amyloid; glial fibrillary acidic protein
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
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Item ID: 44088
Depositing User: Cheryl Hawkes
Date Deposited: 10 Sep 2015 09:44
Last Modified: 07 Dec 2018 10:34
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