Translational and Clinical Research Institute (PCD, DE, DK, JPT, CMM, AJT), Newcastle University, Newcastle upon Tyne, United Kingdom.
School of Biomedical, Nutrition and Sports Sciences (SJC), Newcastle University, Newcastle upon Tyne, United Kingdom.
Am J Geriatr Psychiatry. 2022 Sep;30(9):964-975. doi: 10.1016/j.jagp.2022.02.003. Epub 2022 Feb 12.
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.
Cross-sectional observational study.
University research center.
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).
Ribonucleic acid sequencing of whole blood. Differentially expressed genes (DEGs) were identified and gene set enrichment analysis was carried out.
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.
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.
本研究旨在探讨阿尔茨海默病（AD）和路易体痴呆（DLB）在轻度认知障碍（MCI）和痴呆阶段的基因表达，以增进我们对疾病病理生理学的理解，并基于 mRNA 表达探索潜在的诊断和预后生物标志物。
横断面观察性研究。
大学研究中心。
路易体 MCI（MCI-LB，n=55）、AD-MCI（MCI-AD，n=19）、DLB（n=38）、AD（n=24）患者和认知正常对照组（n=28）。
全血核糖核酸测序。鉴定差异表达基因（DEGs）并进行基因集富集分析。
与认知正常组相比，MCI-LB/DLB 有 22 个 DEGs，MCI-AD/AD 有 61 个 DEGs。比较两组疾病时也鉴定到 DEGs。在 MCI-AD/AD 中，ANP32A 的表达与认知能力更快下降相关。基因集富集分析显示，MCI-LB/DLB 中 MYC 靶基因和氧化磷酸化相关基因下调；MCI-AD/AD 中免疫和炎症反应相关基因上调；与 MCI-LB/DLB 相比，MCI-AD/AD 中干扰素-α和 -γ 反应相关基因上调。
本研究在 MCI-LB/DLB 和 MCI-AD/AD 中鉴定到多个 DEGs。其中一个 DEG，ANP32A，可能是 AD 的预后标志物。MCI-LB/DLB 中与线粒体功能相关的基因下调。本队列中进一步证实了先前报道的 MCI-AD/AD 中与炎症和免疫反应相关基因的上调。MCI-AD/AD 和 MCI-LB/DLB 之间干扰素反应的差异表明，这些疾病之间外周免疫反应存在关键差异。
