Aβ uptake by non-plaque associated microglia (AAICAD 2012) - Aug 17, 2012 - In mice oral administration of 1-deoxy-1-fluoro- scyllo -inositol, a scyllo- inositol analogue improved spatial memory impairments & associated amyloid pathology in a dose-dependent manner; Study identified scyllo- inositol induced Aβ-containing microglia throughout the cortex & hippocampus of TgCRND8 mice
Preclinical-animal • Alzheimer's Disease
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Alzheimer's Association International Conference on Alzheimer's Disease 2012, 14-19 Jul 2012
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P4-191
Background
The role of microglia in beta-amyloid peptide (Aβ) clearance within the central nervous system of Alzheimer's disease (AD) brain is multi-fold. Both human clinical trials and preclinical mouse models of AD have shown that cerebrospinal fluid (CSF) Aβ levels decrease after treatment with scyllo-inositol. We therefore investigated the role of microglia in mediating Ab uptake following scyllo-inositol treatment within the CNS.
Methods
Disease bearing TgCRND8 mice were treated for one month with 1-deoxy-1-fluoro-scyllo-inositol and analyzed for changes in cognitive function using the Morris Water Maze test and in pathological readout measures including amyloid and Aβ loads.
Results
Oral administration of 1-deoxy-1-fluoro- scyllo -inositol, a scyllo- inositol analogue, to TgCRND8 mice improved spatial memory impairments and associated amyloid pathology in a dose-dependent manner. We report here the identification of scyllo- inositol induced Aβ-containing microglia throughout the cortex and hippocampus of TgCRND8 mice. The number of microglia containing Aβ was 1-deoxy-1-fluoro- scyllo -inositol dose dependant and microglia were not associated with extracellular plaques.
Conclusions
These results reveal a novel role for non-plaque associated microglia in the regulation of cerebral A β levels in a mouse model of AD and may help to explain the decreased CSF Aβ levels after treatment with scyllo- inositol.
IR2
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