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
Current Alzheimer Research
Title:In Vivo Uptake of β-Amyloid by Non-Plaque Associated Microglia
Volume: 9 Issue: 8
Author(s): Cheryl A Hawkes, LeHua Deng, Daniela Fenili, Mark Nitz and JoAnne McLaurin
Affiliation:
Keywords: Alzheimer’s disease, anti-aggregant, transgenic mouse model, Microglia, Immunoblotting, Central nervous system, β-amyloid, Glial fibrillary acidic protein
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.
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Cite this article as:
A Hawkes Cheryl, Deng LeHua, Fenili Daniela, Nitz Mark and McLaurin JoAnne, In Vivo Uptake of β-Amyloid by Non-Plaque Associated Microglia, Current Alzheimer Research 2012; 9 (8) . https://dx.doi.org/10.2174/156720512803251084
DOI https://dx.doi.org/10.2174/156720512803251084 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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