Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017
Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Allen Mariet, Wang Xue, Burgess Jeremy D, Watzlawik Jens, Serie Daniel J, Younkin Curtis S, Nguyen Thuy, Malphrus Kimberly G, Lincoln Sarah, Carrasquillo Minerva M, Ho Charlotte, Chakrabarty Paramita, Strickland Samantha, Murray Melissa E, Swarup Vivek, Geschwind Daniel H, Seyfried Nicholas T, Dammer Eric B, Lah James J, Levey Allan I, Golde Todd E, Funk Cory, Li Hongdong, Price Nathan D, Petersen Ronald C, Graff-Radford Neill R, Younkin Steven G, Dickson Dennis W, Crook Julia R, Asmann Yan W, Ertekin-Taner Nilüfer
Аннотация
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.
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.