Abstract
We present an integrated delivery technology herein employing the aerosolized method to repurpose thioflavin S for imaging amyloid beta (Abeta) deposits in the retina as a surrogate of Abeta in the brain for early detection of Alzheimer’s disease. The data showed that wild type (WT) mice also have Abeta deposits in the retinae, albeit much less than 5XFAD mice. Further, only in 5XFAD mice, significant Abeta deposits were found associated with retinal ganglion cells (RGCs) in whole-mount and cross-section data. Furthermore, the fluorescent signal depicted from thioflavin S corroborates with Abeta immunohistochemistry staining information. Overall, this probe delivery via inhalation method is also applicable to other Abeta-binding molecules, such as Congo red, curcumin, and thioflavin T. The advantage of imaging retinal amyloid deposits compared to the brain counterparts is that the eye is easily accessible by in vivo imaging and it reduces the effort to design a probe that must cross the formidable blood-brain barrier.
Highlights
Introduction published maps and institutional affilAlzheimer’s disease (AD) remains among the very few illnesses that have been known for over a century, but remains without a clear and effective method for diagnosis and to date, there is no approved disease-modifying therapeutic
Generating a Thioflavin S (ThioS) aerosolized formulation, we demonstrate the compound can bind and report amyloid beta (Abeta) deposits in a retinae of transgenic mouse model of AD
The presented methodology will open up a new avenue for in vivo application of ThioS and many related Abeta-binding compounds, such as Congo red, thioflavin T or targeted probes, capable of the detection of soluble Abeta oligomers to improve early AD diagnosis [44]
Summary
Introduction published maps and institutional affilAlzheimer’s disease (AD) remains among the very few illnesses that have been known for over a century, but remains without a clear and effective method for diagnosis and to date, there is no approved disease-modifying therapeutic. Since the formation of Abeta is one of the underlying mechanisms implicated in AD, detection of Abeta pathology, at the early stage, would be a real impetus for the treatment and assessing the response to therapy. iations.
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