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Author Notes:

Corresponding Author Contact Information: Mayo Clinic, Departments of Neurology and Neuroscience, 4500 San Pablo Road, Birdsall 3, Jacksonville, FL 32224. taner.nilufer@mayo.edu, Phone: 904-953-7103, FAX: 904-953-7353.

Equal contribution: MA and XW

We thank the patients and their families for their participation, without whom these studies would not have been possible.

We thank the Petrucelli lab for the gift of the anti-tau antibody.

Dr. Petersen has acted as a consultant for Roche, Inc., Merck, Inc., Biogen, Inc. and Genentech, Inc.

Dr. Graff-Radford has multicenter treatment study grants from Lilly, TauRx and consulted for Cytox.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences & Neurology
  • Proteinopathies
  • Alzheimer's disease
  • Progressive supranuclear palsy
  • Myelination
  • Coexpression networks
  • Transcriptome
  • Temporal cortex
  • Cerebellum
  • PROGRESSIVE SUPRANUCLEAR PALSY
  • GENOME-WIDE ASSOCIATION
  • WHITE-MATTER INTEGRITY
  • GENE-EXPRESSION
  • DNA METHYLATION
  • TRANSCRIPTOME
  • NEUROPATHOLOGY
  • VARIANTS
  • RISK
  • OLIGODENDROCYTES

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

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Journal Title:

Alzheimer's and Dementia

Volume:

Volume 14, Number 3

Publisher:

, Pages 352-366

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2017 The Authors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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