A Selection of Important Genes and Their Correlated Behavior in Alzheimer’s Disease

Abstract

In 2017, approximately 5 million Americans were living with Alzheimer’s disease (AD), and it is estimated that by 2050 this number could increase to 16 million. In this study, we apply mathematical optimization to approach microarray analysis to detect differentially expressed genes and determine the most correlated structure among their expression changes. The analysis of GSE4757 microarray dataset, which compares expression between AD neurons without neurofibrillary tangles (controls) and with neurofibrillary tangles (cases), was casted as a multiple criteria optimization (MCO) problem. Through the analysis it was possible to determine a series of Pareto efficient frontiers to find the most differentially expressed genes, which are here proposed as potential AD biomarkers. The Traveling Sales Problem (TSP) model was used to find the cyclical path of maximal correlation between the expression changes among the genes deemed important from the previous stage. This leads to a structure capable of guiding biological exploration with enhanced precision and repeatability. Ten genes were selected (FTL, GFAP, HNRNPA3, COX1, ND2, ND3, ND4, NUCKS1, RPL41, and RPS10) and their most correlated cyclic structure was found in our analyses. The biological functions of their products were found to be linked to inflammation and neurodegenerative diseases and some of them had not been reported for AD before. The TSP path connects genes coding for mitochondrial electron transfer proteins. Some of these proteins are closely related to other electron transport proteins already reported as important for AD.

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

“…In US, there were approximately five million AD cases in 2017, and this number of AD cases is predicted to rise to 16 million by 2050. It is estimated that 1 out of 85 people worldwide would be diagnosed with AD by 2050 [24,25]. Patients with AD experience a slow but gradual decline in memory, thinking, and reasoning skills, with the accompanying dementia that gradually increases in severity, leading eventually to the patient's death.…”

Nucks1 gene polymorphism rs823114 is associated with the positive symptoms and neurocognitive function of patients with schizophrenia in parts of southern China

“…It has been shown to be related to inflammatory immune responses and DNA damage ( Markkanen et al ., 2016 ; Howes and McCutcheon, 2017 ; Watkins and Andrews, 2016 ). Nucks1 is a vertebrate-specific gene ( Bai et al ., 2017 ) that has been indicated that the response to DNA damage by HR is important and plays a role in inflammatory immune response ( Cruz-Rivera et al ., 2018 ). It has been shown that nucks1 is related to several nervous system diseases, including BD ( Fries et al ., 2017 ), AD ( Cruz-Rivera et al ., 2018 ) and PD ( Zhu et al ., 2018 , Liu et al ., 2011 , Vacic et al ., 2014 ).…”

“…Nucks1 is a vertebrate-specific gene ( Bai et al ., 2017 ) that has been indicated that the response to DNA damage by HR is important and plays a role in inflammatory immune response ( Cruz-Rivera et al ., 2018 ). It has been shown that nucks1 is related to several nervous system diseases, including BD ( Fries et al ., 2017 ), AD ( Cruz-Rivera et al ., 2018 ) and PD ( Zhu et al ., 2018 , Liu et al ., 2011 , Vacic et al ., 2014 ). To date, the association between the nucks1 gene and schizophrenia has not been reported.…”

“…Nucks1 has recently been confirmed to be important for homologous recombination (HR) and genomic stability ( Parplys et al ., 2015 ). Additionally, nucks1 has also been determined to be a potential susceptibility gene for certain neurodevelopmental and neurodegenerative diseases, such as bipolar disorder (BD) ( Fries et al ., 2017 ), Alzheimer’s disease (AD) ( Cruz-Rivera et al ., 2018 ) and Parkinson’s disease (PD) ( Vacic et al ., 2014 ; Liu et al ., 2011 ; Zhu et al ., 2018 ). Recently, there has been robust and replicable evidence for genetic variation near the miR-137 gene in schizophrenia ( Yin et al ., 2014 ; Ma et al ., 2014 ; Xu et al ., 2020 ).…”

RPL41 sensitizes retinoblastoma cells to chemotherapeutic drugs via ATF4 degradation

“…Irrespective of their essential roles in ribosome assembly and protein translation, multiple ribosomal proteins possess extraribosomal functions that are closely related to tumor initiation, inflammatory response, and neurodegenerative diseases (Cruz‐Rivera et al, 2018; Doherty et al, 2010; Zhou et al, 2015). Rpl41 has been identified as a tumor suppressor gene, and its deficiency, downregulation, or mutations have been detected in tumors (A. Wang et al, 2011).…”