Hyperspectral Imaging Signatures Detect Amyloidopathy in Alzheimer's Mouse Retina Well before Onset of Cognitive Decline

Amyloidopathic disorders such as Alzheimer's disease present symptomology years after the entrenchment of amyloidogenic imbalance. The pathologic alpha-helix -> beta-strand conversion of amyloid beta(1-42) and amyloid beta(1-40) peptides causes neuronal death in the vicinity. Symptomology often presents only after significant neurodegeneration. This thus warrants early detection of amyloidopathy in Alzheimer's disease. Nonexistent modalities for direct identification and quantitation of soluble amyloid aggregates or (proto)fibrils forced us to undertake the development of a spectrophotometric technique to support ongoing drug design. Key requirements were independence from the need for extraneous staining, unambiguous amyloid aggregate detection, and minimal influence of interpretative errors. A Cytoviva instrument pivotal to this study captures scattering of light of visible-near-infrared (VNIR, 400-1000 nm) wavelengths within each pixel of the microscopic view field. We thus assembled a scattering intensity pattern database that provided signatures of amyloid aggregates. Comparison of unknown samples against this database enabled direct detection of amyloid aggregates. The technique was found useful for monitoring retinal and brain amyloidopathy in an ongoing preclinical anti-AD study, attesting to the technique's sensitivity and specificity. Interestingly, the technique was found applicable not just to excised brain tissue but also to isolated mouse retina. With the retina being heralded widely as a (diagnostic) extension of the CNS and retinal amyloidopathy occurring well before that in the brain, this development raises a possibility for the first direct retinal imaging diagnosis of early asymptomatic Alzheimer's disease.