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

Mariet Allen; Xue Wang; Jeremy D. Burgess; Jens Watzlawik; Daniel J. Serie; Curtis S. Younkin; Thuy Nguyen; Kimberly G. Malphrus; Sarah Lincoln; Minerva M. Carrasquillo; Charlotte Ho; Paramita Chakrabarty; Samantha Strickland; Melissa E. Murray; Vivek Swarup; Daniel H. Geschwind; Nicholas T. Seyfried; Eric B. Dammer; James J. Lah; Allan I. Levey; Todd E. Golde; Cory Funk; Hongdong Li; Nathan D. Price; Ronald C. Petersen; Neill R. Graff-Radford; Steven G. Younkin; Dennis W. Dickson; Julia R. Crook; Yan W. Asmann; Nilüfer Ertekin-Taner

doi:10.1016/j.jalz.2017.09.012

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

Mariet Allen, Xue Wang, Jeremy D. Burgess, Jens Watzlawik, Daniel J. Serie, Curtis S. Younkin, Thuy Nguyen, Kimberly G. Malphrus, Sarah Lincoln, Minerva M. Carrasquillo, Charlotte Ho, Paramita Chakrabarty, Samantha Strickland, Melissa E. Murray, Vivek Swarup, Daniel H. Geschwind, Nicholas T. Seyfried, Eric B. Dammer, James J. Lah, Allan I. LeveyTodd E. Golde, Cory Funk, Hongdong Li, Nathan D. Price, Ronald C. Petersen, Neill R. Graff-Radford, Steven G. Younkin, Dennis W. Dickson, Julia R. Crook, Yan W. Asmann, Nilüfer Ertekin-Taner

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

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.

Original language	English
Pages (from-to)	352-366
Number of pages	15
Journal	Alzheimer's and Dementia
Volume	14
Issue number	3
DOIs	https://doi.org/10.1016/j.jalz.2017.09.012
State	Published - Mar 2018
Externally published	Yes

Keywords

Alzheimer's disease
Cerebellum
Coexpression networks
Myelination
Progressive supranuclear palsy
Proteinopathies
Temporal cortex
Transcriptome

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10.1016/j.jalz.2017.09.012

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Allen, M., Wang, X., Burgess, J. D., Watzlawik, J., Serie, D. J., Younkin, C. S., Nguyen, T., Malphrus, K. G., Lincoln, S., Carrasquillo, M. M., Ho, C., Chakrabarty, P., Strickland, S., Murray, M. E., Swarup, V., Geschwind, D. H., Seyfried, N. T., Dammer, E. B., Lah, J. J., ... Ertekin-Taner, N. (2018). Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases. Alzheimer's and Dementia, 14(3), 352-366. https://doi.org/10.1016/j.jalz.2017.09.012

@article{4117617705704b11850a0d1d81ac6732,

title = "Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases",

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.",

keywords = "Alzheimer's disease, Cerebellum, Coexpression networks, Myelination, Progressive supranuclear palsy, Proteinopathies, Temporal cortex, Transcriptome",

author = "Mariet Allen and Xue Wang and Burgess, {Jeremy D.} and Jens Watzlawik and Serie, {Daniel J.} and Younkin, {Curtis S.} and Thuy Nguyen and Malphrus, {Kimberly G.} and Sarah Lincoln and Carrasquillo, {Minerva M.} and Charlotte Ho and Paramita Chakrabarty and Samantha Strickland and Murray, {Melissa E.} and Vivek Swarup and Geschwind, {Daniel H.} and Seyfried, {Nicholas T.} and Dammer, {Eric B.} and Lah, {James J.} and Levey, {Allan I.} and Golde, {Todd E.} and Cory Funk and Hongdong Li and Price, {Nathan D.} and Petersen, {Ronald C.} and Graff-Radford, {Neill R.} and Younkin, {Steven G.} and Dickson, {Dennis W.} and Crook, {Julia R.} and Asmann, {Yan W.} and Nil{\"u}fer Ertekin-Taner",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2018",

month = mar,

doi = "10.1016/j.jalz.2017.09.012",

language = "English",

volume = "14",

pages = "352--366",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc.",

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Allen, M, Wang, X, Burgess, JD, Watzlawik, J, Serie, DJ, Younkin, CS, Nguyen, T, Malphrus, KG, Lincoln, S, Carrasquillo, MM, Ho, C, Chakrabarty, P, Strickland, S, Murray, ME, Swarup, V, Geschwind, DH, Seyfried, NT, Dammer, EB, Lah, JJ, Levey, AI, Golde, TE, Funk, C, Li, H, Price, ND, Petersen, RC, Graff-Radford, NR, Younkin, SG, Dickson, DW, Crook, JR, Asmann, YW & Ertekin-Taner, N 2018, 'Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases', Alzheimer's and Dementia, vol. 14, no. 3, pp. 352-366. https://doi.org/10.1016/j.jalz.2017.09.012

TY - JOUR

T1 - Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases

AU - Allen, Mariet

AU - Wang, Xue

AU - Burgess, Jeremy D.

AU - Watzlawik, Jens

AU - Serie, Daniel J.

AU - Younkin, Curtis S.

AU - Nguyen, Thuy

AU - Malphrus, Kimberly G.

AU - Lincoln, Sarah

AU - Carrasquillo, Minerva M.

AU - Ho, Charlotte

AU - Chakrabarty, Paramita

AU - Strickland, Samantha

AU - Murray, Melissa E.

AU - Swarup, Vivek

AU - Geschwind, Daniel H.

AU - Seyfried, Nicholas T.

AU - Dammer, Eric B.

AU - Lah, James J.

AU - Levey, Allan I.

AU - Golde, Todd E.

AU - Funk, Cory

AU - Li, Hongdong

AU - Price, Nathan D.

AU - Petersen, Ronald C.

AU - Graff-Radford, Neill R.

AU - Younkin, Steven G.

AU - Dickson, Dennis W.

AU - Crook, Julia R.

AU - Asmann, Yan W.

AU - Ertekin-Taner, Nilüfer

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Cerebellum

KW - Coexpression networks

KW - Myelination

KW - Progressive supranuclear palsy

KW - Proteinopathies

KW - Temporal cortex

KW - Transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85033698535&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2017.09.012

DO - 10.1016/j.jalz.2017.09.012

M3 - Article

C2 - 29107053

AN - SCOPUS:85033698535

SN - 1552-5260

VL - 14

SP - 352

EP - 366

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 3

ER -

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

Abstract

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