Abstract
We initiated the systematic profiling of the dorsolateral prefrontal cortex obtained from a subset of autopsied individuals enrolled in the Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP), which are jointly designed prospective studies of aging and dementia with detailed, longitudinal cognitive phenotyping during life and a quantitative, structured neuropathologic examination after death. They include over 3,322 subjects. Here, we outline the first generation of data including genome-wide genotypes (n=2,090), whole genome sequencing (n=1,179), DNA methylation (n=740), chromatin immunoprecipitation with sequencing using an anti-Histone 3 Lysine 9 acetylation (H3K9Ac) antibody (n=712), RNA sequencing (n=638), and miRNA profile (n=702). Generation of other omic data including ATACseq, proteomic and metabolomics profiles is ongoing. Thanks to its prospective design and recruitment of older, non-demented individuals, these data can be repurposed to investigate a large number of syndromic and quantitative neuroscience phenotypes. The many subjects that are cognitively non-impaired at death also offer insights into the biology of the human brain in older non-impaired individuals.
Highlights
Background & SummaryAlzheimer’s disease (AD) is a common neurodegenerative disease of older age with extensive heterogeneity in its onset and course
The samples that we have profiled come from two prospective studies of aging-The Religious order Study (ROS) and the Memory and Aging Project (MAP)-that recruit older individuals without known dementia and include (1) detailed cognitive, neuroimaging and other ante-mortem phenotyping and (2) an autopsy at the time of death that includes a structured neuropathologic examination
Both studies are run by the same team of investigators at the Rush Alzheimer Disease Center (RADC), and they were designed to be used in joint analyses to maximize sample size
Summary
Alzheimer’s disease (AD) is a common neurodegenerative disease of older age with extensive heterogeneity in its onset and course. The samples that we have profiled come from two prospective studies of aging-The Religious order Study (ROS) and the Memory and Aging Project (MAP)-that recruit older individuals without known dementia and include (1) detailed cognitive, neuroimaging and other ante-mortem phenotyping and (2) an autopsy at the time of death that includes a structured neuropathologic examination. Both studies are run by the same team of investigators at the Rush Alzheimer Disease Center (RADC), and they were designed to be used in joint analyses to maximize sample size. We look forward to this large set of molecular and phenotypic data being repurposed by the neuroscience and other communities of researchers
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