Nature Comm. Paper
“Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques” is a paper reported by Carlo Condello, et al. in the January 29, 2015 issue of Nature Communications (see abstract below).
HiLyte™ Fluor labeled β-Amyloid peptides were used in high resolution confocal and in vivo two-photon imaging in Alzheimer Disease (AD) mouse models to show the interaction between microglia barrier and the accumulation of neurotoxic protofibrillar Aβ hotspots. HiLyte™ Fluor 555 labeled β-amyloid (1-40) and (1-42) and HiLyte™ Fluor 488 labeled β-amyloid (1-40) from AnaSpec were some of the reagents used. These fluorescently labeled peptides were confirmed to be mostly monomeric by SDS-PAGE. To view the entire list of AnaSpec’s HiLyte™ Fluor labeled β-Amyloid peptides, please click here.
Abstract of paper
In Alzheimer’s disease (AD), β-amyloid (Aβ) plaques are tightly enveloped by microglia processes, but the significance of this phenomenon is unknown. Here we show that microglia constitute a barrier with profound impact on plaque composition and toxicity. Using high-resolution confocal and in vivo two-photon imaging in AD mouse models, we demonstrate that this barrier prevents outward plaque expansion and leads to compact plaque microregions with low Aβ42 affinity. Areas uncovered by microglia are less compact but have high Aβ42 affinity, leading to the formation of protofibrillar Aβ42 hotspots that are associated with more severe axonal dystrophy. In ageing, microglia coverage is reduced leading to enlarged protofibrillar Aβ42 hotspots and more severe neuritic dystrophy. CX3CR1 gene deletion or anti-Aβ immunotherapy causes expansion of microglia coverage and reduced neuritic dystrophy. Failure of the microglia barrier and the accumulation of neurotoxic protofibrillar Aβ hotspots may constitute novel therapeutic and clinical imaging targets for AD.