Changes in methylation patterns of multiple genes from peripheral blood leucocytes of Alzheimer's disease patients

2013 ◽  
Vol 25 (2) ◽  
pp. 66-76 ◽  
Author(s):  
Yaping Hou ◽  
Huayun Chen ◽  
Qiong He ◽  
Wei Jiang ◽  
Tao Luo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Normal Population ◽  
Cpg Islands ◽  
Methylation Pattern ◽  
Control Group ◽  
Specific Pcr

BackgroundEfforts aiming at identifying biomarkers and corresponding methods for early diagnosis of Alzheimer's disease (AD) might be the most appropriate strategy to initiate promising new treatments and/or prevention of ADObjectiveThe aim of our study is to assess the association of DNA methylation pattern of various leucocyte genes with AD pathogenesis in order to find potential biomarkers and corresponding methods for molecular diagnosis of AD.MethodsDNA methylation level of various genes in AD patients and normal population were compared by bisulphite sequencing PCR and methylation-specific PCR (MSP). Furthermore, real-time PCR was used to explore the effects of DNA methylation on the expression of target genes.ResultsResults showed significant hypermethylation of mammalian orthologue of Sir2 (SIRT1) gene in AD patients compared with normal population. Meanwhile, changes in methylation level of SIRT1 gene between different severities of AD were also found. Specific primers were designed from the SIRT1 CpG islands to differentiate AD and control group by MSP method. Besides, significant demethylation of β-amyloid precursor protein (APP) gene was observed in AD patients, whereas no difference was observed in other AD-related genes. Moreover, significant decrease in expression of SIRT1 gene and increase in expression of APP gene were also found in AD patients. In addition, the expression level of SIRT1/APP genes was associated with the severity, but not with the age or gender, of AD patients.Conclusion:SIRT1 and APP might be the interesting candidate biomarkers and valuable for clinical diagnosis or treatment of AD.

scholarly journals Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease

2015 ◽  
Vol 5 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Tomoyuki Nagata ◽  
Nobuyuki Kobayashi ◽  
Jumpei Ishii ◽  
Shunichiro Shinagawa ◽  
Ritsuko Nakayama ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Methylation Level ◽  
Clinical Presentation ◽  
Neuropsychological Test ◽  
Cpg Sites ◽  
The Brain ◽  
Normal Controls ◽  
Methylation Ratio

Background/Aims: In the present study, we examined whether DNA methylation of the brain-derived neurotrophic factor (BDNF) promoter is associated with the manifestation and clinical presentation of Alzheimer's disease (AD). Methods: Of 20 patients with AD and 20 age-matched normal controls (NCs), the DNA methylation of the BDNF promoter (measured using peripheral blood samples) was completely analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were compared statistically. Next, we investigated the correlation between the DNA methylation levels and the clinical presentation of AD. Results: The total methylation ratio (in %) of the 20 CpG sites was significantly higher in the AD patients (5.08 ± 5.52%) than in the NCs (2.09 ± 0.81%; p < 0.05). Of the 20 CpG sites, the methylation level at the CpG4 site was significantly higher in the AD subjects than in the NCs (p < 0.05). Moreover, the methylation level was significantly and negatively correlated with some neuropsychological test subscores (registration, recall, and prehension behavior scores; p < 0.05). Conclusion: These results suggest that the DNA methylation of the BDNF promoter may significantly influence the manifestation of AD and might be associated with its neurocognitive presentation.

scholarly journals DNA methylation of AHCY may increase the risk of ischemic stroke

2020 ◽  
Author(s):  
Lei Zhao ◽  
Xiaosheng Chen ◽  
Shengjun Zhou ◽  
Zhiqing Lin ◽  
Xi Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Ischemic Stroke ◽  
Methylation Level ◽  
Age Groups ◽  
Area Under The Curve ◽  
Methylation Pattern ◽  
Control Group ◽  
Case Group ◽  
Roc Curve Analysis ◽  
Gene Encoding

Genetic factors play an important role in the pathogenesis of ischemic stroke. Of these, epigenetic modifications provide a new direction for the study of ischemic stroke pathogenesis. This study aimed to determine the correlation between DNA methylation of the gene encoding S-adenosylhomocysteine hydrolase (AHCY) and the risk of ischemic stroke in 64 ischemic stroke patients and 138 patients with traumatic brain injury (control group). The methylation level of AHCY was analyzed using quantitative methylation-specific polymerase chain reaction. Statistically significant differences in AHCY methylation levels were observed between the case group [medians (interquartile range): 0.13% (0.09%, 0.27%)] and the control group [0.06% (0.00%, 0.17%), p < 0.0001], and these associations remained significant in both male (p = 0.003) and female (p = 0.0005) subjects. A subgroup analysis by age revealed a considerably higher percentage of methylated AHCY in the case group than the control group in all age groups (age < 60 years, p = 0.007; age ≥ 60 years, p < 0.0001). A receiver operating characteristic (ROC) curve analysis revealed a trend toward a role for AHCY methylation as an indicator of risk in all ischemic patients [area under the curve (AUC) = 0.70, p = 0.0001], male patients (AUC = 0.67, p = 0.004), and female patients (AUC = 0.75, p = 0.0002). Our study confirmed a significant association between the AHCY DNA methylation level and the risk of ischemic stroke, suggesting that this gene methylation pattern may be a potential diagnostic marker of ischemic stroke.

scholarly journals Influence of DAT1 Promotor Methylation on Sports Performance

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1425
Author(s):  
Anna Grzywacz ◽  
Krzysztof Chmielowiec ◽  
Agnieszka Boroń ◽  
Monika Michałowska-Sawczyn ◽  
Jolanta Chmielowiec ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cpg Islands ◽  
Epigenetic Mechanism ◽  
Control Group ◽  
Sports Performance ◽  
European Origin ◽  
Specific Pcr ◽  
Dat1 Gene ◽  
Male Subjects

In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factors (TFs) to DNA. As there are still many questions concerning the role of methylation in creating personality, we concentrated on searching for such associations. The research group was 100 sports male subjects (mean age = 22.88, SD = 6.35), whereas the control group included 239 healthy male volunteers matched for age (mean age = 21.69, SD = 3.39), both of European origin. The methods used in our research were as follows: DNA isolation, methylation-specific PCR, sequencing chromatophores, all conducted according to the manufacturer’s procedure. To evaluate personality traits, the NEO Five-Factor Personality Inventory (NEO-FFI) and STAI Inventory were used. We observed the existence of a statistically significant correlation for all the aspects of personality covered and CpG islands’ methylation. Nonetheless, we think that the tested group and the number of tested promotor islands in the DAT1 gene are still too small to make explicit conclusions, so it needs further profound analysis.

DNA methylation level of the neprilysin promoter in Alzheimer's disease brains

2018 ◽  
Vol 670 ◽  
pp. 8-13 ◽  
Author(s):  
Kenichi Nagata ◽  
Tatsuo Mano ◽  
Shigeo Murayama ◽  
Takaomi C. Saido ◽  
Atsushi Iwata
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Methylation Level

scholarly journals DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

Brain ◽  
2013 ◽  
Vol 136 (10) ◽  
pp. 3018-3027 ◽  
Author(s):  
Jose V. Sanchez-Mut ◽  
Ester Aso ◽  
Nicolas Panayotis ◽  
Ira Lott ◽  
Mara Dierssen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Human Brain ◽  
Target Genes

Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

2019 ◽  
Vol 16 (9) ◽  
pp. 834-835
Author(s):  
Petter Järemo ◽  
Alenka Jejcic ◽  
Vesna Jelic ◽  
Tasmin Shahnaz ◽  
Homira Behbahani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cell Damage ◽  
Control Group ◽  
Red Cell ◽  
Oxygen Release ◽  
Regulatory Pathways ◽  
Β Amyloid ◽  
2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

GSK3β 5'-flanking DNA Methylation and Expression in Alzheimer’s Disease Patients

2017 ◽  
Vol 14 (7) ◽  
Author(s):  
Vincenzina Nicolia ◽  
Viviana Ciraci ◽  
Rosaria A. Cavallaro ◽  
Isidre Ferrer ◽  
Sigfrido Scarpa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation

scholarly journals DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Miren Altuna ◽  
Amaya Urdánoz-Casado ◽  
Javier Sánchez-Ruiz de Gordoa ◽  
María V. Zelaya ◽  
Alberto Labarga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Human Hippocampus

scholarly journals Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shingo Tsuji ◽  
Takeshi Hase ◽  
Ayako Yachie-Kinoshita ◽  
Taiko Nishino ◽  
Samik Ghosh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Learning ◽  
Drug Target ◽  
Target Genes ◽  
Drug Repositioning ◽  
Therapeutic Targets ◽  
Machine Learning Techniques ◽  
Computational Framework ◽  
Novel Therapeutic

Abstract Background Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel therapeutic targets. Fortunately, the human protein-protein interaction network (PIN) could be a useful resource to achieve this objective. Methods In this study, we developed a deep learning-based computational framework that extracts low-dimensional representations of high-dimensional PIN data. Our computational framework uses latent features and state-of-the-art machine learning techniques to infer potential drug target genes. Results We applied our computational framework to prioritize novel putative target genes for Alzheimer’s disease and successfully identified key genes that may serve as novel therapeutic targets (e.g., DLG4, EGFR, RAC1, SYK, PTK2B, SOCS1). Furthermore, based on these putative targets, we could infer repositionable candidate-compounds for the disease (e.g., tamoxifen, bosutinib, and dasatinib). Conclusions Our deep learning-based computational framework could be a powerful tool to efficiently prioritize new therapeutic targets and enhance the drug repositioning strategy.

scholarly journals Women have Farther to Fall: Gender Differences Between Normal Elderly and Alzheimer's Disease in Verbal Memory Engender Better Detection of Alzheimer's Disease in Women

2011 ◽  
Vol 17 (4) ◽  
pp. 654-662 ◽  
Author(s):  
Robert M. Chapman ◽  
Mark Mapstone ◽  
Margaret N. Gardner ◽  
Tiffany C. Sandoval ◽  
John W. McCrary ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gender Differences ◽  
Verbal Memory ◽  
Control Group ◽  
Large Drop ◽  
Delayed Recall ◽  
Logical Memory ◽  
Wechsler Memory Scale ◽  
Immediate Recall

AbstractWe analyzed verbal episodic memory learning and recall using the Logical Memory (LM) subtest of the Wechsler Memory Scale-III to determine how gender differences in AD compare to those seen in normal elderly and whether or not these differences impact assessment of AD. We administered the LM to both an AD and a Control group, each comprised of 21 men and 21 women, and found a large drop in performance from normal elders to AD. Of interest was a gender interaction whereby the women's scores dropped 1.6 times more than the men's did. Control women on average outperformed Control men on every aspect of the test, including immediate recall, delayed recall, and learning. Conversely, AD women tended to perform worse than AD men. Additionally, the LM achieved perfect diagnostic accuracy in discriminant analysis of AD versus Control women, a statistically significantly higher result than for men. The results indicate the LM is a more powerful and reliable tool in detecting AD in women than in men. (JINS, 2011, 17, 654–662)

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