• Liana G Apostolova, Chris Zarow, Kristina Biado, Sona Hurtz, Marina Boccardi, Johanne Somme, Hedieh Honarpisheh, Anna E Blanken, Jenny Brook, Spencer Tung, Darrick Lo, Denise Ng, Jeffry R Alger, Harry V Vinters, Martina Bocchetta, Henri Duvernoy, Clifford R Jack, Giovanni B Frisoni, and EADC-ADNI Working Group on the Harmonized Protocol for Manual Hippocampal Segmentation.
• Department of Neurology, UCLA, Los Angeles, CA, USA. Electronic address: lapostolova@mednet.ucla.edu.
• Alzheimers Dement. 2015 Feb 1; 11 (2): 139-50.

ObjectiveThe pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).MethodsTemporal 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 (Aβ), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aβ, and tau burden for each hippocampal subfield were obtained.ResultsWe found significant correlations between hippocampal volume and Braak and Braak staging (ρ = -0.75, P = .001), tau (ρ = -0.53, P = .034), Aβ burden (ρ = -0.61, P = .012), and neuronal count (ρ = 0.77, P < .001). Exploratory subfield-wise significant associations were found for Aβ in Cornu Ammonis (CA)1 (ρ = -0.58, P = .019) and subiculum (ρ = -0.75, P = .001), tau in CA2 (ρ = -0.59, P = .016), and CA3 (ρ = -0.5, P = .047), and neuronal count in CA1 (ρ = 0.55, P = .028), CA3 (ρ = 0.65, P = .006), and CA4 (ρ = 0.76, P = .001).ConclusionsThe observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP.Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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