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. 2015 Feb;11(2):139-50.
doi: 10.1016/j.jalz.2015.01.001. Epub 2015 Jan 22.

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

Liana G Apostolova  1 , Chris Zarow  2 , Kristina Biado  3 , Sona Hurtz  4 , Marina Boccardi  5 , Johanne Somme  6 , Hedieh Honarpisheh  7 , Anna E Blanken  8 , Jenny Brook  9 , Spencer Tung  3 , Darrick Lo  3 , Denise Ng  3 , Jeffry R Alger  8 , Harry V Vinters  10 , Martina Bocchetta  11 , Henri Duvernoy  12 , Clifford R Jack Jr  13 , Giovanni B Frisoni  14 ; EADC-ADNI Working Group on the Harmonized Protocol for Manual Hippocampal Segmentation
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Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol

Liana G Apostolova et al. Alzheimers Dement. 2015 Feb.

Abstract

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 (Aβ), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aβ, and tau burden for each hippocampal subfield were obtained.

Results: We 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).

Conclusions: The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP.

Keywords: Alzheimer; Amyloid; Atrophy; Braak; CERAD; Dementia; Hippocampal atrophy; Hippocampal segmentation; Hippocampal volumes; Hippocampus; Neuronal count; Pathology; Subfields; Tau; validation.

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Figures

Fig. 1
Fig. 1
Scatterplot graphs of pathology distribution by Braak and Braak stage.
Fig. 2
Fig. 2
Scatterplot graphs showing the correlation between hippocampal volume defined by the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Center (EADC-ADNI) Harmonized Protocol (HaRP) and pathology indices (outliers removed for mean amyloid beta [Aβ], Aβ subiculum, and tau CA3).
Fig. 3
Fig. 3
The ratio of median subfield amyloid beta (Aβ) and tau burden, and neuronal count between the groups.
See this image and copyright information in PMC

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