Multispectral cellular-level retinal imaging for early detection of Alzheimer’s disease

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Project Summary/Abstract Physical Sciences Inc (PSI) proposes to develop a novel technique to identify amyloid β-protein (Aβ) deposits in the retina as a biomarker for Alzheimer's disease (AD). Our goal in this program is to develop an optical imaging technique capable of identifying specific chemical compounds in vivo in the retina with cellular-level resolution, non-invasively, and without the use of contrast agents. We will validate the ability of this technique to identify early indications of AD on mice first in Phase I as a proof-of-principle demonstration, and then on humans in Phase II. Although AD cannot yet be treated with the intent to cure, sufficiently early diagnosis will facilitate intervention with available therapeutics, adding years of productive quality time to the patient's life. However, the lack of suitable diagnostic tools for both in vivo rapid screening of Aβ aggregation and early detection of AD pathology poses severe limitations. Current available structural, functional, and metabolic brain imaging methods are not yet suitable for repeated population screening in the preclinical stages. They are either limited by the use of unsafe ionizing isotopes (radioactivity), involve high costs, have low availability, and provide reduced resolution or specificity. An alternative non-invasive approach to visualize Aβ plaques in AD patients could be high-resolution optical imaging of the retina, knowing that Aβ plaques form in retinal layers and share properties with those in the brain. The retina, as an extension of the brain, is the only part of the central nervous system that can be imaged non-invasively at sub-cellular resolutions. Human postmortem histopathological studies have shown accumulation of Aβ in the retinas of those with confirmed AD, principally in the inner-retinal layers. Studies of transgenic mouse models of AD have demonstrated the presence of retinal Aβ and shown quantitative and temporal correlations between brain and retinal Aβ deposition. Most of the in vivo retinal imaging techniques involved fluorescence imaging based on curcumin as a fluorescence tag or on hyperspectral imaging. However, so far, no in vivo retinal imaging technique involving spectral analysis provided cellular-level resolution and no high-resolution retinal imaging instrument possessed spectral discrimination. PSI proposes to develop a multispectral adaptive optics-based non-invasive optical imaging technique that will enable in vivo cellular-level resolution for early detection of Aβ presence in the retina and will facilitate a path to understanding the onset of various neurodegenerative diseases. We will build on our expertise in high-resolution retinal imaging and spectral analysis.