Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol.

Objective: The pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP). Methods: Temporal lobes of nine Alzheimer's disease (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla. Hippocampal volumes were obtained with HarP. Six-micrometer-thick hippocampal slices were stained for amyloid beta (A beta), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, A beta, and tau burden for each hippocampal stibfield were obtained. Results: We found significant correlations between hippocampal volume and Braak and Braak staging (rho = -0.75, P = .001), tau (rho = -0.53, P = .034), A beta burden (rho = -0.61, P = .012), and neuronal count (rho = 0.77, P < .001). Exploratory subfield-wise significant associations were found for All in Cornu Ammonis (CA)1 (rho = -0.58, P = .019) and subiculum (rho = -0.75, P = .001), tau in CA2 (rho = -0.59, P = .016), and CA3 (rho = -0.5, P = .047), and neuronal count in CA1 (rho = -0.55, P = .028), CA3 (rho = -0.65, P = .006), and CA4 (rho = -0.76, P = .001). Conclusions: The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.