COMPARATIVE ANALYSIS OF PIB IN VIVO WITH 6-CN-PIB AND Aβ-IMMUNOHISTOCHEMISTRY POSTMORTEM IN FAMILIAL ALZHEIMER DISEASE ASSOCIATED WITH THE PSEN1 I229F MUTATION

Abstract

low numbers of participants, relatively long intervals between imaging and death, and low level of detail in terms of the spatial patterns of brain atrophy. The purpose of this investigation was to assess the neuropathologic correlates of regional brainvolumes by combining ex-vivoMRvolumetry and pathology on a large community cohort of older persons. Methods: Cerebral hemispheres were obtained from 166 deceased participants of two longitudinal, epidemiologic clinical-pathologic cohort studies of aging. All hemispheres were imaged ex-vivo, while immersed in 4% formaldehyde solution, on a 3T MRI scanner. A multi-atlas approach was used to segment ex-vivo MRI data intowhite and gray matter, and graymatter into 34 cortical and 8 subcortical regions. The volumes of all regions were normalized by the height of the participants. Following imaging, hemispheres underwent neuropathologic examination. The pathologies that were considered in analyses were: Alzheimer’s disease (AD) pathology, Lewy bodies, hippocampal sclerosis, gross and microscopic chronic infarcts, and cerebral amyloid angiopathy. Multiple linear regression was used to investigate the link between regional volumes and neuropathologies, controlling for age at death, sex, education, postmortem interval to fixation and to imaging. False Discovery Rate (FDR) was used to correct for multiple comparisons.Results: Figure 1 shows brain regions with significant negative correlation (p<0.05, FDR-corrected) between their volume and AD pathology (Fig.1A), and hippocampal sclerosis (Fig.1B). No other pathologies showed significant correlations with the volume of the segmented regions. Conclusions: The present study provides information on the neuropathologic correlates of regional brain volumes in a community cohort of older adults, and may help in the development of imaging biomarkers of AD pathology and hippocampal sclerosis. To our knowledge, this is the largest MR volumetry pathology investigation to date, and the only assessing a high number of brain regions.