Reducing amyloid-β (Aβ) accumulation is a promising strategy for developing
Alzheimer’s Disease (AD) therapeutics. We recently reported that a triphenylmethane
food dye analog, Brilliant Blue G (BBG), is a dose-dependent modulator of
in vitro amyloid-β aggregation and cytotoxicity in cell-based assays. Following up on
this recent work, we sought to further evaluate this novel modulator in a therapeutically-relevant AD transgenic mouse
model. BBG was orally administered to APPSwDI/NOS2-/- mice for three months in order to assess its biocompatibility,
its permeability across the blood-brain barrier, and its efficacy at rescuing AD pathology. The results showed that BBG
was well-tolerated, caused no significant weight change/unusual behavior, and was able to significantly cross the AD
blood-brain barrier in APPSwDI/NOS2-/- mice. Immunohistochemical and electron microscopic analysis of the brain sections
revealed that BBG was able to significantly prevent neuronal loss and reduce intracellular APP/Aβ in hippocampal
neurons. This is the first report of 1) the effect of Brilliant Blue G on neuronal loss in a transgenic animal model of AD, 2)
oral administration of BBG to affect a protein conformation/aggregation disease, and 3) electron microscopic ultrastructural
analysis of AD pathology in APPSwDI/NOS2-/- mice.
Keywords: Alzheimer’s Disease, amyloid-β, blood-brain barrier, intracellular amyloid-β, neuronal loss, triphenylmethane dye.
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