Feasibility Study for Detection of Retinal Amyloid in Clinical Trials: The Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Trial

Abstract

AbstractBackgroundAlterations to the retina manifest in patients diagnosed with neurodegenerative diseases such as Alzheimer’s disease (AD). Retinal imaging techniques open the possibility for non‐invasive evaluation of AD pathology. Clinically AD diagnosed patients exhibit retinal amyloid deposits. Few studies monitoring preclinical individuals exist, limiting the assessment of the feasibility of retinal imaging as a biomarker for early‐stage AD risk detection.MethodWe compared retinal and cerebral amyloid in clinically normal individuals who screened positive for high amyloid levels through positron emission tomography (PET) from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) as well as a companion cohort of individuals who exhibited low levels of amyloid PET in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. We quantified the number of curcumin‐positive fluorescent retinal spots from a small subset of participants from both studies to determine retinal amyloid deposition at baseline.ResultParticipants from the A4 trial exhibited a greater number of retinal spots compared to those from the LEARN study. We report a positive correlation between retinal spots and brain amyloid, as measured by the standardized uptake value ratio (SUVr).ConclusionThe results of this small pilot study support the use of retinal fundus imaging for detecting amyloid deposition that is correlated with brain amyloid PET SUVr. A larger sample size will be necessary to fully ascertain the relationship between amyloid PET and retinal amyloid both cross‐sectionally and longitudinally.