Blood mRNA Expression in Alzheimer's Disease and Dementia With Lewy Bodies

Donaghy, Paul C.; Cockell, Simon; Martin‐Ruiz, Carmen; Coxhead, Jonathan; Kane, Joseph; Erskine, Daniel; Koss, David J.; Taylor, John‐Paul; Morris, Christopher M.; O’Brien, John; Thomas, Alan

doi:10.1016/j.jagp.2022.02.003

Cited by 12 publications

(8 citation statements)

References 45 publications

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“…They discovered a significant difference in the expression of AKAP6, which is associated with cognitive function. Donaghy et al (2022) examined the gene expression differences between AD and Dementia with Lewy Bodies (DLB) in both the MCI and dementia stages. They identified multiple DEGs, among which ANP32A was identified as a potential prognostic marker for AD.…”

Section: Identification Of Shared Candidate Biomarkers Between Ad And...mentioning

confidence: 99%

A review and analysis of key biomarkers in Alzheimer’s disease

Zhang,

Liu,

Zhang

et al. 2024

Front. Neurosci.

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects over 50 million elderly individuals worldwide. Although the pathogenesis of AD is not fully understood, based on current research, researchers are able to identify potential biomarker genes and proteins that may serve as effective targets against AD. This article aims to present a comprehensive overview of recent advances in AD biomarker identification, with highlights on the use of various algorithms, the exploration of relevant biological processes, and the investigation of shared biomarkers with co-occurring diseases. Additionally, this article includes a statistical analysis of key genes reported in the research literature, and identifies the intersection with AD-related gene sets from databases such as AlzGen, GeneCard, and DisGeNet. For these gene sets, besides enrichment analysis, protein–protein interaction (PPI) networks utilized to identify central genes among the overlapping genes. Enrichment analysis, protein interaction network analysis, and tissue-specific connectedness analysis based on GTEx database performed on multiple groups of overlapping genes. Our work has laid the foundation for a better understanding of the molecular mechanisms of AD and more accurate identification of key AD markers.

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Section: Identification Of Shared Candidate Biomarkers Between Ad And...mentioning

confidence: 99%

A review and analysis of key biomarkers in Alzheimer’s disease

Zhang,

Liu,

Zhang

et al. 2024

Front. Neurosci.

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“…In healthy brains, the UPP tags damaged proteins with ubiquitin and facilitates their removal with proteosomes [77]. Downregulation of UCHL-1 (ubiquitin C-terminal hydrolase L1), PRKN (parkin RBR E3 ubiquitin protein ligase), SNCAIP (synuclein alpha interacting protein), and USP9Y (ubiquitin specific peptidase 9 Y-linked), all of which translate to proteins within the UPP, have been identified in DLB [78][79][80][81]. The products of these genes contribute to protein tagging, protein degradation, and regulation of the UPP [78][79][80][81].…”

Section: Protein Degredationmentioning

confidence: 99%

“…Downregulation of UCHL-1 (ubiquitin C-terminal hydrolase L1), PRKN (parkin RBR E3 ubiquitin protein ligase), SNCAIP (synuclein alpha interacting protein), and USP9Y (ubiquitin specific peptidase 9 Y-linked), all of which translate to proteins within the UPP, have been identified in DLB [78][79][80][81]. The products of these genes contribute to protein tagging, protein degradation, and regulation of the UPP [78][79][80][81]. Reduced expression of these genes likely contributes to a dysfunctional UPP and protein degradation, and precipitates DLB pathogenesis.…”

Section: Protein Degredationmentioning

confidence: 99%

“…Transcriptomic analysis has also identified possible biomarkers in the biological fluids of DLB cases. Analysis of blood mRNA expression within DLB has identified 17 DEGs that, if replicated, may hold diagnostic biomarker potential [81]. It has also been shown that the expression levels of SNCA transcripts in blood may be utilised to distinguish between DLB and other forms of dementia [69].…”

Section: Other Transcriptomic Signaturesmentioning

confidence: 99%

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Dementia with Lewy Bodies: Genomics, Transcriptomics, and Its Future with Data Science

Goddard,

Brookes,

Sharma

et al. 2024

Cells

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Dementia with Lewy bodies (DLB) is a significant public health issue. It is the second most common neurodegenerative dementia and presents with severe neuropsychiatric symptoms. Genomic and transcriptomic analyses have provided some insight into disease pathology. Variants within SNCA, GBA, APOE, SNCB, and MAPT have been shown to be associated with DLB in repeated genomic studies. Transcriptomic analysis, conducted predominantly on candidate genes, has identified signatures of synuclein aggregation, protein degradation, amyloid deposition, neuroinflammation, mitochondrial dysfunction, and the upregulation of heat-shock proteins in DLB. Yet, the understanding of DLB molecular pathology is incomplete. This precipitates the current clinical position whereby there are no available disease-modifying treatments or blood-based diagnostic biomarkers. Data science methods have the potential to improve disease understanding, optimising therapeutic intervention and drug development, to reduce disease burden. Genomic prediction will facilitate the early identification of cases and the timely application of future disease-modifying treatments. Transcript-level analyses across the entire transcriptome and machine learning analysis of multi-omic data will uncover novel signatures that may provide clues to DLB pathology and improve drug development. This review will discuss the current genomic and transcriptomic understanding of DLB, highlight gaps in the literature, and describe data science methods that may advance the field.

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“…One study of mRNA expression from whole blood collected in vivo found upregulation in TNF-α signaling via the NFκB pathway and the Inflammatory response pathway in DLB (although not statistically significant) and AD on gene set enrichment analyses [106]. Differences in IFN-α and IFN-γ response pathways between DLB and AD were also detected.…”

Section: Transcriptomicsmentioning

confidence: 99%

Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review

Loveland,

Yu,

Churilov

et al. 2023

IJMS

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Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson’s disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.

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Blood mRNA Expression in Alzheimer's Disease and Dementia With Lewy Bodies

Cited by 12 publications

References 45 publications

A review and analysis of key biomarkers in Alzheimer’s disease

A review and analysis of key biomarkers in Alzheimer’s disease

Dementia with Lewy Bodies: Genomics, Transcriptomics, and Its Future with Data Science

Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review

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