Publication Title
Alzheimers Dement
Document Type
Article
Publication Date
3-1-2018
Keywords
Alzheimer Disease; Brain; Cohort Studies; Computational Biology; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Male; Myelin Sheath; Neurons; Supranuclear Palsy, Progressive; Transcriptome
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.
Area of Special Interest
Neurosciences (Brain & Spine)
Specialty/Research Institute
Geriatrics
Specialty/Research Institute
Neurosciences
