Cell death and survival pathways in Alzheimer's disease: an integrative hypothesis testing approach utilizing -omic data sets

NEUROBIOLOGY OF AGING

卷:95

Article

Brokaw, Danielle L.¹  Piras, Ignazio S.²  Mastroeni, Diego¹  Weisenberger, Daniel J.³  Nolz, Jennifer¹  Delvaux, Elaine¹  Serrano, Geidy E.⁴  Beach, Thomas G.⁴  Huentelman, Matthew J.²  Coleman, Paul D.¹ 

[1] Arizona State Univ, Banner Neurodegenerat Dis Res Ctr, Tempe, AZ 85281 USA

[2] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA

[3] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90007 USA

[4] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA

关键词: Alzheimer's;    DNA methylation;    Expression;    Transcriptome;    Methylome;    Cell death;    Cell survival;    Bioinformatics;   

DOI  :  10.1016/j.neurobiolaging.2020.06.022

来源: Elsevier

【 摘 要 】

Whether a cell lives or dies is controlled by an array of intercepting and dynamic molecular pathways. Although there is evidence of neuronal loss in Alzheimer's disease (AD) and multiple programmed cell death (PCD) pathways have been implicated in this process, there has been no comprehensive evaluation of the dominant pathway responsible for cell death in AD. Likewise, the relative dominance of survival and PCD pathways in AD remains unclear. Here, we present the results of hypothesis-driven bioinformatic analysis of PCD and survival pathway activation in paired methylation and expression data from the middle temporal gyrus (MTG) as well as expression from laser-captured cells from the MTG and hippocampus. The results not only indicate activation of cell death pathways in AD-of which apoptosis is responsible for the largest fraction of upregulated genes-but also of cell survival pathways. These results are indicative of a complex balance between survival and death pathways in AD that future studies should work to delineate at a single cell level. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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