In Vivo Uptake of β-Amyloid by Non-Plaque Associated Microglia

Author(s): Cheryl A Hawkes, LeHua Deng, Daniela Fenili, Mark Nitz, JoAnne McLaurin.

Journal Name: Current Alzheimer Research

Volume 9 , Issue 8 , 2012

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Abstract:

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.

Keywords: Alzheimer’s disease, anti-aggregant, transgenic mouse model, Microglia, Immunoblotting, Central nervous system, β-amyloid, Glial fibrillary acidic protein

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Article Details

VOLUME: 9
ISSUE: 8
Year: 2012
Page: [890 - 901]
Pages: 12
DOI: 10.2174/156720512803251084
Price: $58

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