title: Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol.
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.
authors.affiliation: Department of Neurology, UCLA, Los Angeles, CA, USA. Electronic address: lapostolova@mednet.ucla.edu.
authors.forename: Liana G
authors.initials: LG
authors.lastname: Apostolova
authors.affiliation: Department of Neurology, USC, Los Angeles, CA, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Zarow
authors.affiliation: Department of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Biado
authors.affiliation: San Francisco State University, San Francisco, CA, USA.
authors.forename: Sona
authors.initials: S
authors.lastname: Hurtz
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine), IRCCS S.Giovanni di Dio- Fatebenefratelli, Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Boccardi
authors.affiliation: Department of Neurology, Alava University Hospital, Victoria-Gasteiz, Spain.
authors.forename: Johanne
authors.initials: J
authors.lastname: Somme
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Hedieh
authors.initials: H
authors.lastname: Honarpisheh
authors.affiliation: Department of Neurology, UCLA, Los Angeles, CA, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Blanken
authors.affiliation: Department of Medicine Statistics Core, UCLA, Los Angeles, CA, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Brook
authors.affiliation: Department of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Tung
authors.affiliation: Department of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Darrick
authors.initials: D
authors.lastname: Lo
authors.affiliation: Department of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Ng
authors.affiliation: Department of Neurology, UCLA, Los Angeles, CA, USA.
authors.forename: Jeffry R
authors.initials: JR
authors.lastname: Alger
authors.affiliation: Department of Neurology, UCLA, Los Angeles, CA, USA; Department of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine), IRCCS S.Giovanni di Dio- Fatebenefratelli, Brescia, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Bocchetta
authors.affiliation: 35 Chemin des Relançons, Besançon, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Duvernoy
authors.affiliation: Department of Diagnostic Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine), IRCCS S.Giovanni di Dio- Fatebenefratelli, Brescia, Italy; University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001284:Atrophy / Q000473:pathology; D048588:Benzoxazines; D002452:Cell Count; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D048588:Benzoxazines; C054369:MAPT protein, human; D016875:tau Proteins; C028911:cresyl violet
keywords: Alzheimer; Amyloid; Atrophy; Braak; CERAD; Dementia; Hippocampal atrophy; Hippocampal segmentation; Hippocampal volumes; Hippocampus; Neuronal count; Pathology; Subfields; Tau; validation