Blood mRNA Expression in Alzheimer's Disease and Dementia With Lewy Bodies.
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Authors
Donaghy, Paul C
Cockell, Simon J
Martin-Ruiz, Carmen
Coxhead, Jonathan
Kane, Joseph
Erskine, Daniel
Koss, David
Taylor, John-Paul
Morris, Christopher M
O'Brien, John T
Thomas, Alan J
Publication Date
2022-09Journal Title
Am J Geriatr Psychiatry
ISSN
1064-7481
Publisher
Elsevier BV
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Donaghy, P. C., Cockell, S. J., Martin-Ruiz, C., Coxhead, J., Kane, J., Erskine, D., Koss, D., et al. (2022). Blood mRNA Expression in Alzheimer's Disease and Dementia With Lewy Bodies.. Am J Geriatr Psychiatry https://doi.org/10.1016/j.jagp.2022.02.003
Abstract
OBJECTIVES: The objective of this study was to investigate the expression of genes in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), both at the mild cognitive impairment (MCI) and dementia stages, to improve our understanding of disease pathophysiology and investigate the potential for diagnostic and prognostic biomarkers based on mRNA expression. DESIGN: Cross-sectional observational study. SETTING: University research center. PARTICIPANTS: People with MCI with Lewy bodies (MCI-LB, n=55), MCI-AD (n=19), DLB (n=38), AD (n=24) and a cognitively unimpaired comparison group (n=28). MEASUREMENTS: Ribonucleic acid sequencing of whole blood. Differentially expressed genes (DEGs) were identified and gene set enrichment analysis was carried out. RESULTS: Compared with the cognitively unimpaired group, there were 22 DEGs in MCI-LB/DLB and 61 DEGs in MCI-AD/AD. DEGS were also identified when comparing the two disease groups. Expression of ANP32A was associated with more rapid cognitive decline in MCI-AD/AD. Gene set enrichment analysis identified downregulation in gene sets including MYC targets and oxidative phosphorylation in MCI-LB/DLB; upregulation of immune and inflammatory responses in MCI-AD/AD; and upregulation of interferon-α and -γ responses in MCI-AD/AD compared with MCI-LB/DLB. CONCLUSION: This study identified multiple DEGs in MCI-LB/DLB and MCI-AD/AD. One of these DEGs, ANP32A, may be a prognostic marker in AD. Genes related to mitochondrial function were downregulated in MCI-LB/DLB. Previously reported upregulation of genes associated with inflammation and immune responses in MCI-AD/AD was confirmed in this cohort. Differences in interferon responses between MCI-AD/AD and MCI-LB/DLB suggest that there are key differences in peripheral immune responses between these diseases.
Sponsorship
This work was supported by Alzheimer’s Research UK (Grant Numbers ARUK-PPG2018B008 (PCD) and ARUK-PG3026-13 (AJT)) and the NIHR Newcastle Biomedical Research Centre. JO’B is
supported by the NIHR Cambridge Biomedical Research Centre and the Cambridge Centre for
Parkinson’s Plus Disorders. The funders had no role in study design; the collection, analysis and
interpretation of data; the writing of the report; and the decision to submit the article for
publication.
The authors would like to thank The NIHR Clinical Research Network North East and Cumbria for
their invaluable support with participant recruitment to these studies. We would also like to thank
Ms Helen Kain and Ms Sally Barker for their support in the co-ordination of this research.
Embargo Lift Date
2023-02-28
Identifiers
External DOI: https://doi.org/10.1016/j.jagp.2022.02.003
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333876
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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