Building an Ex Vivo Atlas of the Earliest Brain Regions Affected by Alzheimer's Disease Pathology

Earliest neuropathological changes in Alzheimer?s Disease (AD) emerge in the medial temporal lobe (MTL). In order for MRI biomarkers to detect changes linked specifically to AD pathology (as opposed to aging or other pathological factors) macroscopic patterns of structural change in the MTL must be linked to the underlying neuropathology. To provide such a linkage, we are conducting an autopsy imaging study combining ex vivo MRI and serial histopathology. Information from multiple subjects can be studied by creating a ?population average? atlas of the MTL. We present a groupwise registration approach for constructing the atlas that is able to successfully capture the complex structure of the MTL, and anatomical variability across subjects. This atlas allows us to generate maps of cortical thickness measurements and identify regions in the MTL where structural changes correlate most strongly with AD progression. We show that using this atlas, we are able to find a significant correlation between atrophy and AD pathology in the MTL sub-regions associated with the earliest stages of AD pathology as described by Braak and Braak.