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 α-helix → β-strand conversion of amyloid β1–42 and amyloid β1–40 peptides causes neuronal death in the vicinity. Symptomology often presents only after si...

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Bibliographic Details
Published in:ACS chemical neuroscience 2015-02, Vol.6 (2), p.306-315
Main Authors: More, Swati S, Vince, Robert
Format: Article
Language:English
Subjects:
Alzheimer Disease - diagnosis
Alzheimer Disease - drug therapy
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - genetics
Amyloid beta-Protein Precursor - metabolism
Amyloidosis - metabolism
Amyloidosis - pathology
Animals
Brain - metabolism
Brain - pathology
Cell Line, Tumor
Cognition Disorders - metabolism
Cognition Disorders - pathology
Cytoplasm - metabolism
Disease Models, Animal
Female
Fluorescent Antibody Technique
Humans
Mice, Inbred C57BL
Mice, Transgenic
Models, Neurological
Nootropic Agents - pharmacology
Peptide Fragments - metabolism
Presenilin-1 - genetics
Presenilin-1 - metabolism
Retina - metabolism
Retina - pathology
Spectrophotometry - methods
Treatment Outcome
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Summary:Amyloidopathic disorders such as Alzheimer’s disease present symptomology years after the entrenchment of amyloidogenic imbalance. The pathologic α-helix → β-strand conversion of amyloid β1–42 and amyloid β1–40 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.
ISSN:1948-7193
1948-7193
DOI:10.1021/cn500242z