Liana G Apostolova1, Chris Zarow2, Kristina Biado3, Sona Hurtz4, Marina Boccardi5, Johanne Somme6, Hedieh Honarpisheh7, Anna E Blanken8, Jenny Brook9, Spencer Tung3, Darrick Lo3, Denise Ng3, Jeffry R Alger8, Harry V Vinters10, Martina Bocchetta11, Henri Duvernoy12, Clifford R Jack13, Giovanni B Frisoni14. 1. Department of Neurology, UCLA, Los Angeles, CA, USA. Electronic address: lapostolova@mednet.ucla.edu. 2. Department of Neurology, USC, Los Angeles, CA, USA. 3. Department of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA. 4. San Francisco State University, San Francisco, CA, USA. 5. LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine), IRCCS S.Giovanni di Dio- Fatebenefratelli, Brescia, Italy. 6. Department of Neurology, Alava University Hospital, Victoria-Gasteiz, Spain. 7. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. 8. Department of Neurology, UCLA, Los Angeles, CA, USA. 9. Department of Medicine Statistics Core, UCLA, Los Angeles, CA, USA. 10. Department of Neurology, UCLA, Los Angeles, CA, USA; Department of Pathology & Laboratory Medicine, UCLA, Los Angeles, CA, USA. 11. 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. 12. 35 Chemin des Relançons, Besançon, France. 13. Department of Diagnostic Radiology, Mayo Clinic and Foundation, Rochester, MN, USA. 14. LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine), IRCCS S.Giovanni di Dio- Fatebenefratelli, Brescia, Italy; University Hospitals and University of Geneva, Geneva, Switzerland.
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.
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.
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