Altered expression of mitochondrial genes involved in energy production and mitochondrial biogenesis is related to an increase in inflammatory factors associated with Alzheimer's disease: Molecular and cell biology/mitochondrial function/energetics. (7th December 2020)

• Record Type: Journal Article
• Authors: Castora, Frank J.; Slocum, Jayne A.; Knoble, Joseph A.; Kerns, Kimberly A.; Hitefield, Naomi L.; Gershon, Blake; Shugoll, Jason; Coleman, Randolph A.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 2
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.046328
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that presents with symptoms such as cognitive impairment and a decline in memory. While often characterized by amyloid plaques and neurofibrillary tangles, there are a number of factors that play a role in this chronic disease. Recent studies have shown that mitochondrial function, and particularly, cytochrome oxidase (COX) activity is decreased in AD, disrupting mitochondrial energy production and potentially contributing to neurodegeneration. More recently, studies have indicated that inflammation plays an important role in the development of neurodegenerative diseases such as AD. Here, we analyzed changes in expression of 162 genes involved in mitochondrial energy production and biogenesis from 16 brain samples (11 AD and 5 age‐matched controls) and examined our findings through the lens of correlating any mitochondrial gene changes with inflammation processes. Method: Total RNA was isolated from 80‐180 mg of frozen brain tissue from the 16 samples. Total RNA was quantified and assessed for purity using Nanodrop and Bioanalyzer analysis. cDNA was prepared and applied to the Human Mitochondrial Energy Metabolism and the Mitochondria RT² Profiler™ PCR Arrays. The qPCR data was then analyzed using Qiagen RT 2 Profiler PCR Array Data Analysis version 3.5. The fold regulation and p‐value data was input into Ingenuity Pathway Analysis software to identify biologically important networks and pathways affected by AD. Result: Three energy metabolism genes – ATP4A, ATP6VIG3, and NDUFA8 – were found to be strongly up‐regulated in AD vs control brains while 6 mitochondrial biogenesis genes – UCP3, TIMM22, SLC25A21, SLC25A23, SLC25A25 and TIMM9 – were found to be strongly downregulated. Furthermore, two transcriptional regulators, RICTOR and KDM5A were activated while upstream regulators PPARGC1A and RB1 were inhibited in the AD vs control samples. The observed changes in mitochondrial gene expression in our data set were associated with neurodegeneration and inflammatory response networks. Conclusion: Gene expression data revealed an overall increase in inflammatory activity in AD brains compared to control brains. Further studies are needed to determine the clinical application of these findings, as an anti‐inflammatory approach to AD directed at mitochondrial genes/proteins could potentially slow the development or onset of the disease