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

Hawkes, Cheryl A. and Deng, LeHua H. and Fenili, Daniela and Nitz, Mark and McLaurin, JoAnne A. (2012) In vivo uptake of β-amyloid by non-plaque associated microglia. Current Alzheimer Research, 9 (8). pp. 890-901. ISSN 1567-2050

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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.

Item Type:
Journal Article
Journal or Publication Title:
Current Alzheimer Research
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2728
Subjects:
ID Code:
137311
Deposited By:
Deposited On:
07 Oct 2019 08:40
Refereed?:
Yes
Published?:
Published
Last Modified:
29 Jul 2020 06:03