Using imaging biomarkers in the histological validation of Alzheimer's disease

Abstract

Without a cure for Alzheimer's disease (AD), early diagnosis and reliable prognosis through validation of biomarkers is critical in preventing irreversible brain damage and abnormal changes in the brain. Iron is readily visible in T2* MRI, and has been shown to be spatially correlated with amyloid beta (Aβ) plaques. Neurofibrillary tangles of tau protein are also associated with AD. We examined the spatial relationship between tau, Aβ, and iron accumulations in the entorhinal cortex of 3 serial sections in 2 subjects. This area is the first, and eventually one of the most heavily damaged neocortical area in AD, and thus would be an excellent area of the brain to visualize anatomic changes in early stages of the disease. Using OlyVIA software and Photoshop, we superimposed and registered all 3 sections with their corresponding stains for comparison and visualization of how the markers are localized in space. Our findings show correlations between both tau and Aβ depositions with Fe accumulations. Established patterns of similarity between Aβ, tau, and/or iron will serve as biomarkers on an MRI, permitting earlier predictions concerning the onset of AD.Grant Funding Source: NIH/NIA 1 R21 AG037843‐02, NIH/NCRR P41 RR013642‐12S1, Translational Research Fund (UCLA), and the McGinty Family Foundation