Transcriptomic and epigenomic landscapes of Alzheimer's disease evidence mitochondrial-related pathways

Alejandro Marmolejo-Garza, Tiago Medeiros-Furquim, Ramya Rao, Bart J L Eggen, Erik Boddeke*, Amalia M Dolga*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)
95 Downloads (Pure)

Abstract

Alzheimer's Disease (AD) is the main cause of dementia and it is defined by cognitive decline coupled to extracellular deposit of amyloid-beta protein and intracellular hyperphosphorylation of tau protein. Historically, efforts to target such hallmarks have failed in numerous clinical trials. In addition to these hallmark-targeted approaches, several clinical trials focus on other AD pathological processes, such as inflammation, mitochondrial dysfunction, and oxidative stress. Mitochondria and mitochondrial-related mechanisms have become an attractive target for disease-modifying strategies, as mitochondrial dysfunction prior to clinical onset has been widely described in AD patients and AD animal models. Mitochondrial function relies on both the nuclear and mitochondrial genome. Findings from omics technologies have shed light on AD pathophysiology at different levels (e.g., epigenome, transcriptome and proteome). Most of these studies have focused on the nuclear-encoded components. The first part of this review provides an updated overview of the mechanisms that regulate mitochondrial gene expression and function. The second part of this review focuses on evidence of mitochondrial dysfunction in AD. We have focused on published findings and datasets that study AD. We have focused on published findings and datasets that study AD. We analyzed published data and provide examples for mitochondrial-related pathways. These pathways are strikingly dysregulated in AD neurons and glia in sex-, cell- and disease stage-specific manners. Analysis of mitochondrial omics data highlights the involvement of mitochondria in AD, providing a rationale for further disease modeling and drug targeting.

Original languageEnglish
Article number 119326
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1869
Issue number10
Early online date14-Jul-2022
DOIs
Publication statusPublished - Oct-2022

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