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IC‐O3–04: In vivo characterization of glutamatergic vulnerability in behavioral variant FTD: An [11C]ABP688 PET/ VBM /DBM study
Author(s) -
Leuzy Antoine,
Rowley Jared,
Cheewakriengkrai Laksanun,
Shin Monica,
Wang Seqian,
Parent Maxime,
Zimmer Eduardo,
Dauar Marina,
RosaNeto Pedro,
Gauthier Serge
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.04.029
Subject(s) - neuroscience , voxel , binding potential , frontotemporal dementia , white matter , pittsburgh compound b , atrophy , positron emission tomography , medicine , psychology , voxel based morphometry , audiology , nuclear medicine , pathology , dementia , cognitive impairment , radiology , cognition , magnetic resonance imaging , disease
Background: Pathological examination of the brain is used to confirm Alzheimer’s disease (AD) diagnosis. In AD, the second earliest site where pathology occurs after the entorhinal cortex is the hippocampus. Hippocampal atrophy is the most established AD imaging biomarker.Methods:Temporal lobes of 10 deceased AD subjects and 5 deceased cognitively normal controls (NC) were obtained from the AD Research Center Brain Bank at the University of California, Los Angeles and scanned with a Bruker Biospec 7 Tesla MRI machine at the UCLA Brain Mapping Center. Hippocampal MRI scans were manually registered to the International Consortium for Brain Mapping template. Hippocampal structures were manually traced and converted into 3D mesh models. Radial distance maps and volumes were computed for each hippocampal structure. Temporal lobes were sectioned coronally in 5mm blocks, embedded in paraffin and cut into 6 mm slices, mounted, and stained for amyloid beta 40, tau, and Cresyl Violet. Aperio ScanScope CS was used to scan the slides digitally at 20x. The CA1 hippocampal subfield was manually traced. To quantify disease burden in the CA1 subfield, in-house nuclear and positively immunostaining pixel algorithms were used to determine neuronal counts and amyloid beta 40 and tau burden. Results: We found significant correlations between amyloid beta 40 burden and hippocampal volume (r1⁄4-0.55, p corrected 1⁄40.035) andmean hippocampal radial distance (r1⁄4-0.58, p corrected1⁄40.025). In addition, neuronal count per CA1 m m 2 was positively correlated with mean radial distance (r1⁄40.61, p corrected 1⁄40.016). Conclusions: As expected, our findings suggest that amyloid burden is inversely related to hippocampal volume and radial distance. Lower CA1 neuronal count also showed a significant association with hippocampal atrophy. The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD pathology.