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


Type
Article
Change log
Authors
Donaghy, Paul C 
Cockell, Simon J 
Martin-Ruiz, Carmen 
Coxhead, Jonathan 
Kane, Joseph 
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.

Description
Keywords
ANP32A, RNA, alzheimer's disease, dementia with Lewy bodies, inflammation, mild cognitive impairment, Alzheimer Disease, Cognitive Dysfunction, Cross-Sectional Studies, Humans, Lewy Body Disease, Nuclear Proteins, RNA, Messenger, RNA-Binding Proteins
Journal Title
Am J Geriatr Psychiatry
Conference Name
Journal ISSN
1064-7481
1545-7214
Volume Title
Publisher
Elsevier BV
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.