![]() ![]() The approach used in constructing these traits is described in detail elsewhere 1, 2 and can be applied to specific cognitive domains, e.g., episodic memory decline, one of the hallmarks of AD. 19 different neuropsychologic tests are common between ROS and MAP (of the 21 tests deployed by one or the other study), and these data are collapsed into a single “Global Cognitive Score.” The longitudinal Global Cognitive Scores are then used in a random effects model to estimate person-specific annual rates of cognitive decline controlling for known confounders such as demographics and years of education. It is derived from the annual neuropsychologic evaluation of each subject. The primary trait that captures this trajectory of decline is the “Global Cognitive Slope”. Cross-sectional assessment of cognitive performance at the last clinical evaluation can be used in analyses with neuropathology or brain omics data however, the trajectory of cognitive decline is a more pertinent trait for drug discovery as this is the clinical outcome of interest in the vast majority of clinical trials both in the preclinical and clinical AD space. We refer to the joint dataset as “ROSMAP”. ROS subjects live in communities distributed throughout the U.S., while MAP subjects live in communities in the Chicago metropolitan area. ![]() 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. 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. Thus, new insights into the events leading to AD in the older brain are needed, and new forms of data from the target organ will help to support unbiased assessment that will yield such insights. Despite over three decades of work, there are currently no treatments for AD, and its pathobiology remains incompletely understood. 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.Īlzheimer’s disease (AD) is a common neurodegenerative disease of older age with extensive heterogeneity in its onset and course. 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. Generation of other omic data including ATACseq, proteomic and metabolomics profiles is ongoing. 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). 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.
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