scholarly journals Association and Gene–-Gene Interactions Study of Late-Onset Alzheimer’s Disease in the Russian Population

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1647
Author(s):  
Anna Bocharova ◽  
Kseniya Vagaitseva ◽  
Andrey Marusin ◽  
Natalia Zhukova ◽  
Irina Zhukova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Factor Model ◽  
Late Onset ◽  
Interaction Network ◽  
Russian Population ◽  
Protein Protein Interaction ◽  
Protective Haplotype ◽  
Single Snps

Alzheimer’s disease (AD) is a neurodegenerative disorder, and represents the most common cause of dementia. In this study, we performed several different analyses to detect loci involved in development of the late onset AD in the Russian population. DNA samples from 472 unrelated subjects were genotyped for 63 SNPs using iPLEX Assay and real-time PCR. We identified five genetic loci that were significantly associated with LOAD risk for the Russian population (TOMM40 rs2075650, APOE rs429358 and rs769449, NECTIN rs6857, APOE ε4). The results of the analysis based on comparison of the haplotype frequencies showed two risk haplotypes and one protective haplotype. The GMDR analysis demonstrated three significant models as a result: a one-factor, a two-factor and a three-factor model. A protein–protein interaction network with three subnetworks was formed for the 24 proteins. Eight proteins with a large number of interactions are identified: APOE, SORL1, APOC1, CD33, CLU, TOMM40, CNTNAP2 and CACNA1C. The present study confirms the importance of the APOE-TOMM40 locus as the main risk locus of development and progress of LOAD in the Russian population. Association analysis and bioinformatics approaches detected interactions both at the association level of single SNPs and at the level of genes and proteins.

scholarly journals The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Troy T. Rohn
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Senile Plaques ◽  
Myeloid Cells ◽  
Disease Process ◽  
Age Related

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by a progressive loss of memory and cognitive skills. Although much attention has been devoted concerning the contribution of the microscopic lesions, senile plaques, and neurofibrillary tangles to the disease process, inflammation has long been suspected to play a major role in the etiology of AD. Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD. Variants in TREM2 triple one's risk of developing late-onset AD. TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS. In this context, an overview of the pathways linking beta-amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will be discussed.

scholarly journals Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer’s disease

2018 ◽  
Author(s):  
Stephen A. Semick ◽  
Rahul A. Bharadwaj ◽  
Leonardo Collado-Torres ◽  
Ran Tao ◽  
Joo Heon Shin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Brain Regions ◽  
Epigenetic Mechanism ◽  
Novel Genes ◽  
Age Related

AbstractBackgroundLate-onset Alzheimer’s disease (AD) is a complex age-related neurodegenerative disorder that likely involves epigenetic factors. To better understand the epigenetic state associated with AD represented as variation in DNA methylation (DNAm), we surveyed 420,852 DNAm sites from neurotypical controls (N=49) and late-onset AD patients (N=24) across four brain regions (hippocampus, entorhinal cortex, dorsolateral prefrontal cortex and cerebellum).ResultsWe identified 858 sites with robust differential methylation, collectively annotated to 772 possible genes (FDR<5%, within 10kb). These sites were overrepresented in AD genetic risk loci (p=0.00655), and nearby genes were enriched for processes related to cell-adhesion, immunity, and calcium homeostasis (FDR<5%). We analyzed corresponding RNA-seq data to prioritize 130 genes within 10kb of the differentially methylated sites, which were differentially expressed and had expression levels associated with nearby DNAm levels (p<0.05). This validated gene set includes previously reported (e.g. ANK1, DUSP22) and novel genes involved in Alzheimer’s disease, such as ANKRD30B.ConclusionsThese results highlight DNAm changes in Alzheimer’s disease that have gene expression correlates, implicating DNAm as an epigenetic mechanism underlying pathological molecular changes associated with AD. Furthermore, our framework illustrates the value of integrating epigenetic and transcriptomic data for understanding complex disease.

scholarly journals Investigation of five polymorphic DNA markers associated with late onset Alzheimer disease

Genetika ◽  
2013 ◽  
Vol 45 (2) ◽  
pp. 503-514 ◽  
Author(s):  
Jalal Gharesouran ◽  
Maryam Rezazadeh ◽  
Mohaddes Mojtaba
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Markers ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
The Elderly ◽  
Healthy Controls ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
And Control

Alzheimer's disease is a complex neurodegenerative disorder characterized by memory and cognitive impairment and is the leading cause of dementia in the elderly. The aim of our study was to examine the polymorphic DNA markers CCR2 (+190 G/A), CCR5?32, TNF-? (-308 G/A), TNF-? (-863 C/A) and CALHM1 (+394 C/T) to determine the relationship between these polymorphisms and the risk of late onset Alzheimer's disease in the population of Eastern Azerbaijan of Iran. A total of 160 patient samples and 163 healthy controls were genotyped by PCR-RFLP and the results confirmed using bidirectional sequencing. Statistical analysis of obtained data revealed non-significant difference between frequency of CCR5?32 in case and control groups. The same result was observed for TNF-? (-863 C/A) genotype and allele frequencies. Contrary to above results, significant differences were detected in frequency of TNF-? (-308 G/A) and CCR2-64I genotypes between the cases and healthy controls. A weak significant difference observed between allele and genotype frequencies of rs2986017 in CALHM1 (+394 C/T; P86L) in patient and control samples. It can be concluded that the T allele of P86L variant in CALHM1 & +190 G/A allele of CCR2 have a protective role against abnormal clinical features of Alzheimer's disease.

scholarly journals Drug Repurposing for Alzheimer’s Disease based on Protein-Protein Interaction Network

2021 ◽  
Author(s):  
Negar Sadat Soleimani Zakeri ◽  
Saeid Pashazadeh ◽  
Habib MotieGhader
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Neurodegenerative Disorder ◽  
Gentian Violet ◽  
Interaction Network ◽  
New Drugs ◽  
Bipartite Network ◽  
Medical Studies ◽  
Gene Complexes

Abstract Background: Alzheimer's disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment is vital. This study proposes a method to extract substantial gene complexes and accomplish an enrichment analysis to introduce the most significant biological procedures. The next step is extracting the drugs related to AD and introduce some new drugs which may be useful for this disease. Results: To this end, protein-protein interactions (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. The next step was to construct a five bipartite network representing the genes of each group and their target miRNAs. Finally, a complete network including all the genes related to each gene complex group and genes’ target drug was illustrated. medical studies and publications were analyzed thoroughly to introduce AD-related drugs. Conclusions: This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. RALOXIFENE, GENTIAN VIOLET are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. These two drugs.

A Chronological Review of Potential Disease-Modifying Therapeutic Strategies for Alzheimer's Disease

2020 ◽  
Vol 26 (12) ◽  
pp. 1286-1299 ◽  
Author(s):  
Miren Ettcheto ◽  
Oriol Busquets ◽  
Triana Espinosa-Jiménez ◽  
Ester Verdaguer ◽  
Carme Auladell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Wide Spectrum ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
New Therapeutic Approaches ◽  
Β Protein

: Late-onset Alzheimer’s disease (LOAD) is a neurodegenerative disorder that has become a worldwide health problem. This pathology has been classically characterized for its affectation on cognitive function and the presence of depositions of extracellular amyloid β-protein (Aβ) and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau protein. To this day, no effective treatment has been developed. : Multiple strategies have been proposed over the years with the aim of finding new therapeutic approaches, such as the sequestration of Aβ in plasma or the administration of anti-inflammatory drugs. Also, given the significant role of the insulin receptor in the brain in the proper maintenance of cognitive function, drugs focused on the amelioration of insulin resistance have been proposed as potentially useful and effective in the treatment of AD. In the present review, taking into account the molecular complexity of the disease, it has been proposed that the most appropriate therapeutic strategy is a combinatory treatment of several drugs that will regulate a wide spectrum of the described altered pathological pathways.

scholarly journals Identification of Key Genes Related with Alzheimer’s Disease Treatment Through Bioinformatics Analysis

2018 ◽  
Vol 9 (1) ◽  
pp. 78
Author(s):  
Liqun Wang ◽  
Hongjia Qian ◽  
Liqun Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interaction ◽  
Expression Profiles ◽  
Amyloid Β ◽  
Interaction Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Tg2576 Mice

T0901317, a live X receptor agonist, can reduce amyloid β generation in vitro and in a mouse Alzheimer’s disease (AD) model. To investigate the global molecular effects of T0901317 in mouse hippocampus, we downloaded public GSE31624 generated from the hippocampus of wild-type mice, Tg2576 mice and T0901317-treated Tg2576 mice. Differentially-expressed genes (DEGs) were identified on LIMMA of R software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment were analyzed through DAVID. Protein- protein interaction and hub genes were obtained based on STRING and Cytoscape. Nine downregulated and 68 upregulated DEGs in T0901317-treated Tg2576 were identified in comparison with untreated Tg2576 mice. Annotation analyses showed these DEGs correlated with transport (BP), membrane (CC) and binding (MF) terms and the dopaminergic synapse pathway. Protein-protein interaction network was built to find out some hub genes by maximal clique centrality. Discs large homolog 4 (Dlg4), the most outstanding gene, was associated with cognition improvement in aged AD mice. T0901317 may impact the development by regulating the Dlg4 expression. In conclusion, we investigated effects of T0901317 therapy on gene expression profiles in the hippocampus of Tg2576 mice and found Dlg4 may serve as putative therapeutics target for AD treatment.

scholarly journals Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer’s Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 2071 ◽  
Author(s):  
Jia Xu ◽  
Fang Wang ◽  
Jiejie Guo ◽  
Chunshuang Xu ◽  
Yanzi Cao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Plasticity ◽  
Topological Analysis ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Neuroprotective Effects ◽  
Main Compound ◽  
Protein Protein Interaction ◽  
Alpinia Oxyphylla

Alpinia oxyphylla Miq. (i.e., A. oxyphylla), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer’s disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein–protein interaction network constructions, and the network topological analysis, we concluded that A. oxyphylla may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of A. oxyphylla extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.

scholarly journals Utility of animal models of Alzheimer’s disease in food bioactive research

2021 ◽  
Vol 13 ◽  
Author(s):  
Klaus W. Lange
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Clinical Success ◽  
Treatment Strategies ◽  
New Drugs ◽  
Preclinical Research ◽  
Novel Treatment Strategies

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by globally impaired cognition. AD research in animals has shown a substantial deficit in translational relevance. The most extensively used transgenic mouse models overexpress human genes associated with rare familial early-onset AD, which results in the formation of amyloid plaques. However, the most common form of AD (late-onset sporadic AD) is a multifactorial disorder involving different cytotoxic factors, including neurofibrillary pathology. Transgenic mice studies have been valuable in elucidating pathogenetic mechanisms that may be relevant to human AD. However, their utility in the development of novel treatment strategies and as preclinical testbeds of new drugs has been unsatisfactory. Animal models have so far failed to demonstrate predictive value in regard to novel therapies of AD, including the use of bioactive food components. While many therapeutic approaches assessed in animals have shown promising results, attempts to translate these findings to people with AD have been disappointing. Food scientists should be aware that the available animal models appear to be unable to predict clinical success in humans. Therefore, food bioactive research should focus on human-centric preventive approaches to AD in clinically meaningful settings rather than on highly questionable preclinical research in animals.

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