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Cell BiologybioRxiv

A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research

P. De Jager, Y. Ma, C. McCabe, J. Xu, B. N. Vardarajan, D. Felsky, H.-U. Klein, C. C. White, M. A. Peters, B. Lodgson, P. Nejad, A. Tang, L. M. Mangravite, L. Yu, C. Gaiteri, S. Mostafavi, J. A. Schneider, D. A. Bennett

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 and belong to a very few prospective studies of aging and dementia with detailed, longitudinal cognitive phenotyping during life and a quantitative, structured neuropathologic examination after death for >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.

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