Systematic review of gene expression studies in people with Lewy body dementia

Chowdhury, Anisa; Rajkumar, Anto P

Abstract

Objectives:
Lewy body dementia (LBD) is the second most prevalent neurodegenerative dementia, and it causes more morbidity and mortality than Alzheimer's disease. Several genetic associations of LBD have been reported, and their functional implications remain uncertain. Hence, we aimed to do a systematic review of all gene expression studies that investigated people with LBD for improving our understanding of LBD molecular pathology and for facilitating discovery of novel biomarkers and therapeutic targets for LBD.

Methods:
We systematically reviewed five online databases (PROSPERO protocol: CRD42017080647) and assessed the functional implications of all reported differentially expressed genes (DEG) using Ingenuity Pathway Analyses.

Results:
We screened 3,809 articles and identified 31 eligible studies. 1,242 statistically significant (p[less than]0.05) DEGs including 70 microRNAs have been reported in people with LBD. Expression levels of alternatively spliced transcripts of SNCA, SNCB, PRKN, APP, RELA, and ATXN2 significantly differ in LBD. Several mitochondrial genes and genes involved in ubiquitin proteasome system and autophagy lysosomal pathway were significantly downregulated in LBD. Evidence supporting chronic neuroinflammation in LBD was inconsistent. Our functional analyses highlighted the importance of RNA-mediated gene silencing, neuregulin signalling, and neurotrophic factors in the molecular pathology of LBD.

Conclusions:
α-synuclein aggregation, mitochondrial dysfunction, defects in molecular networks clearing misfolded proteins, and RNA-mediated gene silencing contribute to neurodegeneration in LBD. Larger longitudinal transcriptomic studies investigating biological fluids of people living with LBD are needed for molecular subtyping and staging of LBD. Diagnostic biomarker potential and therapeutic promise of identified DEGs warrant further research.

Citation

Chowdhury, A., & Rajkumar, A. P. (2020). Systematic review of gene expression studies in people with Lewy body dementia. Acta Neuropsychiatrica, 32(6), 281-292. https://doi.org/10.1017/neu.2020.13

• Journal Article Type: Article
• Acceptance Date: Feb 27, 2020
• Online Publication Date: Mar 17, 2020
• Publication Date: 2020-12
• Deposit Date: Feb 28, 2020
• Publicly Available Date: Sep 18, 2020
• Journal: Acta Neuropsychiatrica
• Print ISSN: 0924-2708
• Electronic ISSN: 1601-5215
• Publisher: Cambridge University Press
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 6
• Pages: 281-292
• DOI: https://doi.org/10.1017/neu.2020.13
• Keywords: Biological Psychiatry; Psychiatry and Mental health
• Public URL: https://nottingham-repository.worktribe.com/output/4050681
• Publisher URL: https://www.cambridge.org/core/journals/acta-neuropsychiatrica/article/systematic-review-of-gene-expression-studies-in-people-with-lewy-body-dementia/90D58082CBE2D3F3432F9AABFF1C280F