Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases

• Type of Material: Article
• Authors: Mariet Allen, Mayo Clinic; Xue Wang, Emory University; Jeremy D. Burgess, Mayo Clinic; Jens Watzlawik, Mayo Clinic; Daniel J. Serie, Mayo Clinic; Curtis S. Younkin, Mayo Clinic; Thuy Nguyen, Mayo Clinic; Kimberly G. Malphrus, Mayo Clinic; Sarah Lincoln, Mayo Clinic; Minerva M. Carrasquillo, Mayo Clinic; Charlotte Ho, Mayo Clinic; Paramita Chakrabarty, University of Florida; Samantha Strickland, Mayo Clinic; Melissa E. Murray, Mayo Clinic; Vivek Swarup, University of California Los Angeles; Daniel H. Geschwind, University of California Los Angeles; Nicholas Seyfried, Emory University; Eric Dammer, Emory University; James Lah, Emory University; Allan Levey, Emory University; Todd E. Golde, University of Florida; Cory Funk, Institute for Systems Biology; Hongdong Li, Institute for Systems Biology; Nathan D. Price, Institute for Systems Biology; Ronald C. Petersen, Mayo Clinic; Neill R. Graff-Radford, Mayo Clinic; Steven G. Younkin, Mayo Clinic; Dennis W. Dickson, Mayo Clinic; Julia R. Crook, Mayo Clinic; Yan W. Asmann, Mayo Clinic; Nilufer Ertekin-Taner, Mayo Clinic
• Language: English
• Date: 2018-03-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jalz.2017.09.012
• Title of Journal or Parent Work: Alzheimer's and Dementia
• ISSN: 1552-5260
• Volume: 14
• Issue: 3
• Start Page: 352
• End Page: 366
• Grant/Funding Information: This work was supported by National Institute on Aging [R01 AG032990, RF AG051504 to N.E.T.; U01 AG046139 to N.E.T. and S.G.Y.; P50 AG0016574 to D.W.D, N.E.T, N.R.G.-R., R.C.P. and S.G.Y.]; U01 AG006786 to R.C.P; National Institute of Neurological Disorders and Stroke [R01 NS080820 to N.E.T]; Mayo Clinic Center for Individualized Medicine [Gerstner Family Career Development Award to M.E.M].
• Keywords: Temporal cortex; Proteinopathies; Life Sciences & Biomedicine; Alzheimer's disease; Progressive supranuclear palsy; Neurosciences & Neurology; PROGRESSIVE SUPRANUCLEAR PALSY; WHITE-MATTER INTEGRITY; VARIANTS; GENOME-WIDE ASSOCIATION; OLIGODENDROCYTES; DNA METHYLATION; GENE-EXPRESSION; Cerebellum; Clinical Neurology; TRANSCRIPTOME; Coexpression networks; RISK; NEUROPATHOLOGY; Myelination; Transcriptome; Science & Technology
• Research Categories: Chemistry, Biochemistry; Biology, Neuroscience

Abstract

Introduction: Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways. Methods: We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects. Results: We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples. Discussion: Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks.