Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models

Ying-Wooi Wan, Rami Al-Ouran, Carl Grant Mangleburg, Tom V. Lee, Katherine Allison, Sarah Neuner, Catherine Kaczorowski, Vivek Phillip, Gareth Howell, Heidi Martini-Stoica, Hui Zheng, Jungwoo Wren Kim, Valina Dawson, Ted Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Minghui Wang, Michelle E. Ehrlich, Hongkang Mei, Xiaoyan Zhong, Paramita Chakrabarty, Yona Levites, Todd E. Golde, Allan I. Levey, Accelerating Medicines Partnership-Alzheimer’s Disease Consortium, Benjamin Logsdon, Lara Mangravite, Zhandong Liu, Joshua M. Shulman
doi: https://doi.org/10.1101/506873
Ying-Wooi Wan
1Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
2Jan and Dan Duncan Neurologic Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
24Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rami Al-Ouran
1Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
2Jan and Dan Duncan Neurologic Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
24Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carl Grant Mangleburg
2Jan and Dan Duncan Neurologic Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
24Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tom V. Lee
2Jan and Dan Duncan Neurologic Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
4Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine Allison
2Jan and Dan Duncan Neurologic Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
4Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah Neuner
5The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catherine Kaczorowski
5The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vivek Phillip
5The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gareth Howell
5The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heidi Martini-Stoica
6Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hui Zheng
3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jungwoo Wren Kim
8Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
9Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
10Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Valina Dawson
8Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
9Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
11Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
12Adrienne Helis Malvin & Diana Helis Henry Medical Research Foundations, New Orleans, LA 70130, USA
14Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ted Dawson
8Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
11Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
12Adrienne Helis Malvin & Diana Helis Henry Medical Research Foundations, New Orleans, LA 70130, USA
13Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
14Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ping-Chieh Pao
15The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
16Broad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li-Huei Tsai
15The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
16Broad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Vianney Haure-Mirande
17Departments of Neurology and Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minghui Wang
18Department of Genetics and Genomic Sciences & Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michelle E. Ehrlich
17Departments of Neurology and Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
18Department of Genetics and Genomic Sciences & Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongkang Mei
19Neuroscience DPU, Shanghai R&D, GlaxoSmithKline, Shanghai, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoyan Zhong
19Neuroscience DPU, Shanghai R&D, GlaxoSmithKline, Shanghai, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paramita Chakrabarty
20Evelyn F. and William L. McKnight Brain Institute, Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience and Neurology, University of Florida, Gainesville, FL 32610
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yona Levites
20Evelyn F. and William L. McKnight Brain Institute, Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience and Neurology, University of Florida, Gainesville, FL 32610
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Todd E. Golde
20Evelyn F. and William L. McKnight Brain Institute, Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience and Neurology, University of Florida, Gainesville, FL 32610
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allan I. Levey
21Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin Logsdon
23Sage Bionetworks
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lara Mangravite
23Sage Bionetworks
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhandong Liu
1Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
2Jan and Dan Duncan Neurologic Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Joshua.Shulman@bcm.edu zhandonl@bcm.edu
Joshua M. Shulman
2Jan and Dan Duncan Neurologic Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
4Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
6Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA
24Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Joshua.Shulman@bcm.edu zhandonl@bcm.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

SUMMARY

Human brain transcriptomes can highlight biological pathways associated with Alzheimer’s disease (AD); however, challenges remain to link expression changes with causal triggers. We have examined 30 AD-associated, gene coexpression modules from human brains for overlap with 251 differentially-expressed gene sets from mouse brain RNA-sequencing experiments, including from models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus neurofibrillary tangle pathology and further reveal age- and sex-dependent expression signatures for AD progression. Human coexpression modules enriched for neuronal and/or microglial genes overlap broadly with signatures from mouse models of AD, Huntington’s disease, Amyotrophic Lateral Sclerosis, and also aging. Several human AD coexpression modules, including those implicated in the unfolded protein response and oxidative phosphorylation, were not activated in AD models, but instead were detected following other, unexpected mouse genetic manipulations. Our results comprise a powerful, cross-species resource and pinpoint experimental models for diverse features of AD pathophysiology from human brain transcriptomes.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 03, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models
Ying-Wooi Wan, Rami Al-Ouran, Carl Grant Mangleburg, Tom V. Lee, Katherine Allison, Sarah Neuner, Catherine Kaczorowski, Vivek Phillip, Gareth Howell, Heidi Martini-Stoica, Hui Zheng, Jungwoo Wren Kim, Valina Dawson, Ted Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Minghui Wang, Michelle E. Ehrlich, Hongkang Mei, Xiaoyan Zhong, Paramita Chakrabarty, Yona Levites, Todd E. Golde, Allan I. Levey, Accelerating Medicines Partnership-Alzheimer’s Disease Consortium, Benjamin Logsdon, Lara Mangravite, Zhandong Liu, Joshua M. Shulman
bioRxiv 506873; doi: https://doi.org/10.1101/506873
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models
Ying-Wooi Wan, Rami Al-Ouran, Carl Grant Mangleburg, Tom V. Lee, Katherine Allison, Sarah Neuner, Catherine Kaczorowski, Vivek Phillip, Gareth Howell, Heidi Martini-Stoica, Hui Zheng, Jungwoo Wren Kim, Valina Dawson, Ted Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Minghui Wang, Michelle E. Ehrlich, Hongkang Mei, Xiaoyan Zhong, Paramita Chakrabarty, Yona Levites, Todd E. Golde, Allan I. Levey, Accelerating Medicines Partnership-Alzheimer’s Disease Consortium, Benjamin Logsdon, Lara Mangravite, Zhandong Liu, Joshua M. Shulman
bioRxiv 506873; doi: https://doi.org/10.1101/506873

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4119)
  • Biochemistry (8828)
  • Bioengineering (6532)
  • Bioinformatics (23484)
  • Biophysics (11804)
  • Cancer Biology (9223)
  • Cell Biology (13336)
  • Clinical Trials (138)
  • Developmental Biology (7442)
  • Ecology (11425)
  • Epidemiology (2066)
  • Evolutionary Biology (15173)
  • Genetics (10452)
  • Genomics (14056)
  • Immunology (9187)
  • Microbiology (22198)
  • Molecular Biology (8823)
  • Neuroscience (47625)
  • Paleontology (351)
  • Pathology (1431)
  • Pharmacology and Toxicology (2493)
  • Physiology (3736)
  • Plant Biology (8090)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2224)
  • Systems Biology (6042)
  • Zoology (1254)