Relationship between hippocampal atrophy and neuropathology markers: A 7T MRI validation study of the EADC-ADNI harmonized hippocampal segmentation protocol

Liana G. Apostolova, Chris Zarow, Kristina Biado, Sona Hurtz, Marina Boccardi, Johanne Somme, Hedieh Honarpisheh, Anna E. Blanken, Jenny Brook, Spencer Tung, Emily Kraft, Darrick Lo, Denise Ng, Jeffry R. Alger, Harry V. Vinters, Martina Bocchetta, Henri Duvernoy, Clifford R. Jack, Giovanni B. Frisoni, George BartzokisJohn G. Csernansky, Mony J. De Leon, Leyla Detoledo-Morrell, Ronald J. Killiany, Stephane Lehericy, Nikolai Malykhin, Johannes Pantel, Jens C. Pruessner, Hilkka Soininen, Craig Watson

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)139-150
Number of pages12
JournalAlzheimer's and Dementia
Volume11
Issue number2
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Alzheimer
  • Amyloid
  • Atrophy
  • Braak
  • CERAD
  • Dementia
  • Hippocampal atrophy
  • Hippocampal segmentation
  • Hippocampal volumes
  • Hippocampus
  • Neuronal count
  • Pathology
  • Subfields
  • Tau
  • Validation

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy

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    Apostolova, L. G., Zarow, C., Biado, K., Hurtz, S., Boccardi, M., Somme, J., Honarpisheh, H., Blanken, A. E., Brook, J., Tung, S., Kraft, E., Lo, D., Ng, D., Alger, J. R., Vinters, H. V., Bocchetta, M., Duvernoy, H., Jack, C. R., Frisoni, G. B., ... Watson, C. (2015). Relationship between hippocampal atrophy and neuropathology markers: A 7T MRI validation study of the EADC-ADNI harmonized hippocampal segmentation protocol. Alzheimer's and Dementia, 11(2), 139-150. https://doi.org/10.1016/j.jalz.2015.01.001