1 Transcriptomic profiling of myeloid cells in Alzheimer’s Disease brain illustrates 1 heterogeneity of microglia endolysosomal subtypes 2 3 Katherine E. Prater* 1 (ORCID: 0000-0001-8615-207X), Kevin J. Green* 1 , Wei Sun 2 , Carole L. 4 Smith 1 , Kenneth L. Chiou 3 , Laura Heath 4 , Shannon Rose 5 , C. Dirk Keene 5 , Ronald Y. Kwon 6,7 , 5 Noah Snyder-Mackler (ORCID: 0000-0003-3026-6160) 3 , Elizabeth E. Blue (ORCID: 0000-0002- 6 0633-0305) 9,10 , Jessica E. Young 5,6 , Ali Shojaie 8 , Benjamin Logsdon 4,11 , Gwenn A. Garden 12 , 7 and Suman Jayadev 1,6 8 1 Department of Neurology, University of Washington, Seattle, WA 98195 9 2 Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research 10 Center, Seattle, WA 11 3 School of Life Sciences, Center for Evolution and Medicine, Arizona State University, Tempe, 12 AZ 13 4 Sage Bionetworks, Seattle, WA 14 5 Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 15 6 Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 16 7 Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA 17 8 Department of Biostatistics, University of Washington, Seattle, WA 18 9 Division of Medical Genetics, University of Washington, Seattle, WA 19 10 Brotman Baty Institute for Precision Medicine, Seattle, Washington, 98195, USA 20 11 Cajal Neuroscience, Seattle, WA 21 12 Department of Neurology, University of North Carolina, Chapel Hill, NC 22 * Equal co-first authors 23 24 Key words: AD, microglia, RNAseq, inflammation, human, APOE 25 Correspondence to: 26 Suman Jayadev, MD 27 sumie@uw.edu 28 29 Word Count: 30 Abstract: 147 31 Text: 4756 32 Methods: 1987 33 Figures: 7 34 Tables: 1 35 Supplemental Figures: 2 Tables: 3 36 37 38 Acknowledgements: Funding for these studies was provided by: RF1AG063540 and 39 P30AG066509. Additional support was provided by the Ellison Foundation. Autopsy materials 40 used in this study were obtained from the University of Washington Neuropathology Core, which 41 is supported by the Alzheimer’s Disease Research Center (AG05136) and the Adult Changes in 42 Thought Study (AG006781). Conceived and designed experiments: SJ, KJG, CLS, BL, GAG. 43 Performed the experiments: KJG, CLS, SR, CDK. Analyzed data: KEP, KJG, KLC. Biostatistics 44 oversight: WS, AS. Wrote the manuscript: KEP, KJG, SJ. Edited the manuscript: CLS, WS, 45 EEB, GAG. Provided code: WS, KLC, NSM, RYK, LH. Conceptualized the research and 46 collaborations: SJ, GAG, JEY, EEB, BL. 47 . CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted December 19, 2021. ; https://doi.org/10.1101/2021.10.25.465802 doi: bioRxiv preprint