IC‐P‐184: PATHOLOGIC VALIDATION OF THE EADC‐ADNI HARMONIZED HIPPOCAMPAL PROTOCOL

Background: The gold standard for Alzheimer’s Disease (AD) diagnosis is post-mortem examination of brain tissue. Pathologic validation is the only definitive way to ascertain the validity of disease biomarkers. Hippocampal atrophy is the most established structural imaging biomarker for AD to date. The European Alzheimer9s Disease Consortium and the Alzheimer9s Disease Neuroimaging Initiative investigators recently developed a Harmonized Protocol for Hippocampal Segmentation (EADC-ADNI HarP). EADC-ADNI HarP has not yet been pathologically validated.Methods: The temporal lobes of 9 AD and 7 cognitively normal subjects (NC) were scanned post-mortem at 7 Tesla. Pathologic diagnosis of AD was based on Braak and Braak and CERAD criteria. The temporal lobes were scanned for 60 hours on a 7T Bruker Biospec MRI scanner. Hippocampal volumes were obtained with the EADC-ADNI HarP. 6µm-thick hippocampal slices were stained for amyloid beta (Aβ1-40), tau and cresyl violet. The demarcations of each hippocampal subfield were manually drawn with Aperio ImageScope® CS on the digitally scanned stained tissue. Subfield margins were identified based on cytoarchitectonic features. Neuronal counts, Aβ and tau burden for each hippocampal subfield were obtained.Results: Kruskal-Wallis comparison of medians showed significant differences between the two groups for total hippocampal tau and Aβ burden (p=0.01 for both) but not neuronal count (p=0.12). Significant differences in the medians were also seen in all subfields for tau and in the subiculum, CA1 and CA3 for Aβ. We found significant correlations between hippocampal volume and fresh brain weight (ρ=0.69, p=0.003), Braak and Braak staging (ρ=-0.71, p=0.002), tau (ρ=-0.53, p=0.034) and Aβ burden (ρ=-0.61, p=0.012). Subfield-wise significant association were found for Aβ in CA1 (ρ=-0.58, p=0.019) and subiculum (ρ=-0.75, p=0.001), as well as tau in CA2 (ρ=-0.59, p=0.016) and CA3 (ρ=-0.5, p=0.047).Conclusions: The observed associations provide pathologic validation for the EADC-ADNI HarP and pathologic confirmation of hippocampal morphometry as a valid AD biomarker. Disclosure: Dr. Apostolova has received personal compensation for activities with Eli Lilly & Company. Dr. Zarow has nothing to disclose. Dr. Biado has nothing to disclose. Dr. Babakchanian has nothing to disclose. Dr. Boccardi has received research support from the Alzheimer9s Association, Bioclinica, Brain Image Analysis LLC, Ixico, Roche Diagnostics Corporation, Synarc, and True Positive Medical Devices. Dr. Somme has nothing to disclose. Dr. Honarpisheh has nothing to disclose. Dr. Blanken has nothing to disclose. Dr. Brook has nothing to disclose. Dr. Tung has nothing to disclose. Dr. Ng has nothing to disclose. Dr. Alger has nothing to disclose. Dr. Vinters has nothing to disclose. Dr. Bocchetta has nothing to disclose. Dr. Bocchetta has nothing to disclose. Dr. Duvernoy has nothing to disclose. Dr. Jack has received personal compensation for activities with Janssen, Eisai Inc., General Electric, Johnson & Johnson, and Eli Lilly & Co. Dr. Jack has received research support from Pfizer Inc., Allon, and Baxter. Dr. Frisoni has received personal compensation for activities with Eli Lilly & Company, Bristol-Myers Squibb Company, Bayer, Lundbeck, Elan Corporation, AstraZeneca Corporation, Pfizer Inc, Taurx, Wyeth Pharmaceuticals, and General Electric. Dr. Frisoni has recieved personal compensation in an editorial capacity for Lancet Neurology, Aging Clinical & Experimental Research, Alzheimer9s Diseases & Associated Disorders, Neurodegenerative Diseases, and Neurobiology of Aging. Dr. Frisoni has received research support from Wyeth Pharmaceuticals, Eli Lilly & Company, Lundbeck, General Electric, Avid/Lilly, and the Alzheimer9s Association.