Retinal amyloid fluorescence imaging predicts cerebral amyloid burden and Alzheimer's disease

Background: A practical, inexpensive screening test that could detect and monitor early Alzheimer's disease (AD) pathology, before irreversible brain atrophy occurs, would empower the search for more successful treatments and, in future, identify populations that could benefit from new therapeutics. While AD-related pathology in the brain is well documented, the disease has also been reported to affect the retina, a developmental outgrowth of the brain, which is more accessible for imaging. We describe an eye test for early detection of AD, utilizing Curcumin fluorescence imaging to highlight Aβ aggregates in the retina. This report presents results from analysis of the retinal amyloid test and Pittsburgh Compound B (PiB)-PET imaging from AD, MCI and HC participants in the AIBL research cohort at the McCusker Alzheimer's Research Foundation in Perth, Australia. Methods: The trial involves two visits by volunteers for retinal fluorescence imaging. Between appointments, volunteers take a proprietary Curcumin supplement. Curcumin binds to Aβ with high affinity and has fluorescence properties that enable Aβ plaques to be imaged in the retina. Quantitative analysis of Aβ plaque number, area (mm 2) and distribution is performed from retinal images to create retinal amyloid index (RAI). Blood testing is utilised to determine Curcumin uptake. Results: Preliminary results (n=40) indicate that RAI is highly correlated with brain plaque burden from PET scans (R=0.762, p<0.0001), supporting the hypothesis of hallmark AD pathology in the retina and providing the basis of an ocular screening test for AD. The retinal amyloid test could also differentiate between AD and non-AD with 100% sensitivity and 80.6% specificity. The full study (n=200) is expected to be completed in mid-2014. Conclusions: The retinal amyloid test is a potential initial screen that could compliment currently used brain PET, MRI and clinical psychometric tests, and could potentially be delivered as part of regular eye checks. Micrometer-level imaging resolution could also allow accurate monitoring of individual retinal plaques within AD therapeutic trials.