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