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

Paul C. Donaghy (Lead / Corresponding author), Simon J. Cockell, Carmen Martin-Ruiz, Jonathan Coxhead, Joseph Kane, Daniel Erskine, David Koss, John Paul Taylor, Christopher M. Morris, John T. O'Brien, Alan J. Thomas

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
22 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)964-975
Number of pages12
JournalAmerican Journal of Geriatric Psychiatry
Volume30
Issue number9
Early online date2 Aug 2022
DOIs
Publication statusPublished - Sept 2022

Keywords

  • alzheimer's disease
  • ANP32A
  • dementia with Lewy bodies
  • inflammation
  • mild cognitive impairment
  • RNA

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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