| Autor: |
A Hawkes, Cheryl, Deng, LeHua, Fenili, Daniela, Nitz, Mark, McLaurin, JoAnne |
| Zdroj: |
Current Alzheimer Research; October 2012, Vol. 9 Issue: 8 p890-901, 12p |
| Abstrakt: |
The role of microglia in -amyloid (A) deposition or clearance in the Alzheimers disease (AD) brain remains unclear. Previous in vivo studies have focused primarily on the association of microglia with A-positive parenchymal plaques, but have given little consideration to the possible interaction between A and non-plaque associated microglia. Further, it is not known if microglia play a direct role in mediating A uptake following anti-aggregant treatment. We report here the identification of A-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 A 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 A levels in a mouse model of AD. |
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