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Lookup NU author(s): Dr Paul Donaghy, Dr Simon CockellORCiD, Dr Carmen Martin-RuizORCiD, Dr Jonathan Coxhead, Dr Joseph Kane, Dr Daniel ErskineORCiD, Dr David KossORCiD, Professor John-Paul TaylorORCiD, Dr Christopher Morris, Professor John O'Brien, Professor Alan ThomasORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
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 centre. 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 RNA 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. Conclusions 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.
Author(s): Donaghy PC, Cockell SJ, Martin-Ruiz C, Coxhead J, Kane J, Erskine D, Koss D, Taylor JP, Morris CM, O'Brien JT, Thomas AJ
Publication type: Article
Publication status: Published
Journal: American Journal of Geriatric Psychiatry
Year: 2022
Volume: 30
Issue: 9
Pages: 964-975
Print publication date: 01/09/2022
Online publication date: 12/02/2022
Acceptance date: 03/02/2022
Date deposited: 08/02/2022
ISSN (print): 1064-7481
ISSN (electronic): 1545-7214
Publisher: Elsevier
URL: https://doi.org/10.1016/j.jagp.2022.02.003
DOI: 10.1016/j.jagp.2022.02.003
ePrints DOI: 10.57711/w5vj-ty12
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