scholarly journals 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer’s Disease

2021 ◽  
Author(s):  
Lei Chen ◽  
Shunliang Xu ◽  
Qianqian Shen ◽  
Hongzhuan Yu ◽  
Shengjie Pei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Cell Free Dna ◽  
Cognitively Normal ◽  
Free Dna ◽  
Genome Wide ◽  
Significant Difference ◽  
Normal Controls ◽  
Circulating Cell Free Dna

Abstract Background: 5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in nervous system. It has been reported that 5hmC is significant associated with Alzheimer’s disease (AD). Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. However, there is no research about genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD to date. Methods: We carried out a case-control study and used a highly sensitive and selective high-throughput sequencing of chemical labels to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in AD patients and the control. Results: We detected a significant difference of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls. AD patients can be well distinguished from cognitively normal controls by differentially hydroxymethylated regions (DhMRs) in cfDNA. Specially, we found 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) had prediction diagnostic potential based on their significant correlations with MMSE and MoCA scores. Conclusions: The present results suggest that 5hmC markers derived from plasma cfDNA can be served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100042537, registered 13 January 2021-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120582.

scholarly journals 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Lei Chen ◽  
Qianqian Shen ◽  
Shunliang Xu ◽  
Hongzhuan Yu ◽  
Shengjie Pei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Critical Role ◽  
Cell Free Dna ◽  
Free Dna ◽  
Genome Wide ◽  
A Genome ◽  
Normal Controls ◽  
Circulating Cell Free Dna

Background: 5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in central nervous system. It has been reported that DNA 5hmC dysregulation play a critical role in Alzheimer’s disease (AD) pathology. Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. Objective: However, the genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD has not been reported to date. Methods: We carried out a case-control study and used a genome-wide chemical capture followed by high-throughput sequencing to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in late-onset AD patients and the control. Results: We discovered significant differences of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls, indicating they can be well distinguished from normal controls by DhMRs in cfDNA. Specially, we identified 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) with predicting diagnostic potential based on their significant correlations with MMSE and MoCA scores of subjects. Conclusion: The present results suggest that 5hmC markers derived from plasma cfDNA can served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD.

scholarly journals Genome-Wide DNA Methylation Differences Between Late-Onset Alzheimer's Disease and Cognitively Normal Controls in Human Frontal Cortex

2012 ◽  
Vol 29 (3) ◽  
pp. 571-588 ◽  
Author(s):  
Kelly M. Bakulski ◽  
Dana C. Dolinoy ◽  
Maureen A. Sartor ◽  
Henry L. Paulson ◽  
John R. Konen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Frontal Cortex ◽  
Late Onset ◽  
Cognitively Normal ◽  
Genome Wide ◽  
Human Frontal Cortex ◽  
Normal Controls

scholarly journals Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups

2018 ◽  
Vol 25 (11) ◽  
pp. 2942-2951 ◽  
Author(s):  
Shubhabrata Mukherjee ◽  
◽  
Jesse Mez ◽  
Emily H. Trittschuh ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Disease Diagnosis ◽  
Single Nucleotide ◽  
Cognitively Normal ◽  
Snp Data ◽  
Genotype Frequencies ◽  
Genome Wide ◽  
Ε4 Allele

Abstract Categorizing people with late-onset Alzheimer’s disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer’s disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p < 10−5 and odds ratios more extreme than those previously reported for Alzheimer’s disease (<0.77 or >1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had ≥1 APOE ε4 allele than any other subgroup (overall p = 1.5 × 10−27). Across subgroups, there were 33 novel suggestive loci across the genome with p < 10−5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively defined subgroups and nominate novel genetic loci.

scholarly journals Association study of polymorphisms in ABCA7, clusterin, and MS4A6A genes with Alzheimer’s disease in the Egyptian population

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hanem G. Abd Elrahman ◽  
Abeer Ramadan ◽  
Eman M. Saleh ◽  
Alia A. Saleh ◽  
Noha A. Sabry ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Fragment Length Polymorphism ◽  
Cognitively Normal ◽  
Egyptian Population ◽  
Apo E ◽  
Significant Difference ◽  
Allelic Distribution ◽  
Normal Controls

AbstractAlzheimer’s disease is a genetically heterogeneous brain disease which is associated with a decrease in thinking capacity and changes in personality. Various gene polymorphisms could be associated with the occurrence of Alzheimer’s disease.ObjectivesThis study aimed at exploring the association of ABCA7 rs3764650, CLU rs11136000, and MS4A6A rs610932 genetic variants with AD in a sample of the Egyptian population.MethodsDNA extraction was done from peripheral blood. Genotyping was done using PCR followed by restriction fragment length polymorphism (RFLP) in 100 Alzheimer patients of age 60 years old or above and 100 cognitively normal controls. DNA sequencing was done for eight samples with different genotypes to confirm the results.ResultsNo significant difference was found in genotypic or allelic distribution of CLU rs11136000 between patients and controls. the frequency of CLU CC genotype among AD patients, was lower in Apo E 4 carriers compared to Apo E 4 non-carriers with a significant difference (p=0.003). No significant difference was found in genotypic or allelic distribution of ABCA7 rs3764650 and MS4A6A rs610932 between patients and controls.ConclusionWe concluded that AD not associated with Clustrin rs11136000, ABCA7 rs3764650 and MS4A6A rs610932 genes polymorphism.

scholarly journals Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Brian C.-H. Chiu ◽  
Chang Chen ◽  
Qiancheng You ◽  
Rudyard Chiu ◽  
Girish Venkataraman ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Non Invasive ◽  
Signature Genes ◽  
Non Hodgkin Lymphoma ◽  
Free Dna ◽  
Genome Wide ◽  
Circulating Cell Free Dna

AbstractThe 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.

scholarly journals C-338A Polymorphism of the Endothelin-Converting Enzyme (ECE-1) Gene and the Susceptibility to Sporadic Late-Onset Alzheimer’s Disease and Coronary Artery Disease

2008 ◽  
Vol 24 (3) ◽  
pp. 175-179 ◽  
Author(s):  
Renato Scacchi ◽  
Giuseppe Gambina ◽  
Elisabetta Broggio ◽  
Maria Ruggeri ◽  
Rosa Maria Corbo
Keyword(s):  
Alzheimer’S Disease ◽  
Coronary Artery Disease ◽  
Alzheimer's Disease ◽  
Coronary Artery ◽  
Late Onset ◽  
Protective Role ◽  
Converting Enzyme ◽  
Significant Difference ◽  
Endothelin Converting Enzyme ◽  
Artery Disease

The human endothelin-converting enzyme (ECE) is involved inβ-amyloid synthesis and regulation of the endothelin-1 (ET-1) vasoconstricting peptide. We investigated the distribution of the C-338A polymorphism of the ECE-1b gene in sporadic late-onset Alzheimer’s disease (LOAD) and in coronary artery disease (CAD) to verify its role in the onset of these two complex diseases. Two cohorts of 458 Italian Caucasian LOAD patients and 165 CAD patients were examined for the C-338A polymorphism and compared with respective control samples (260 and 106 subjects, respectively). The A allele was less present in LOAD patients than in controls, but an at limits statistically significant difference was achieved only in subjects aged less than 80 years, where only the AA genotypes appeared to have a protective role against the onset of the sporadic LOAD. For the overall CAD sample the pattern was similar and significant differences were observed only in subjects non carrying the apolipoprotein E (APOE) e*4 allele, where the A allele carrying genotypes had a protective role against the onset of the disease.

Alterations in T-Cell Transcription Factors and Cytokine Gene Expression in Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-21
Author(s):  
Masoud Neshan ◽  
Seyed Kazem Malakouti ◽  
Leila Kamalzadeh ◽  
Mina Makvand ◽  
Arezoo Campbell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcription Factors ◽  
T Cell ◽  
Late Onset ◽  
Cytokine Gene Expression ◽  
Mrna Levels ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ

Background: Late-onset Alzheimer’s disease (LOAD) is associated with many environmental and genetic factors. The effect of systemic inflammation on the pathogenesis of neurodegenerative diseases such as AD has been strongly suggested. T helper cells (Th) are one of the important components of the immune system and can easily infiltrate the brain in pathological conditions. The development of each Th-subset depends on the production of unique cytokines and their main regulator. Objective: This study aimed to compare the mRNA levels of Th-related genes derived from peripheral blood mononuclear cells of LOAD patients with control. Also, the identification of the most important Th1/Th2 genes and downstream pathways that may be involved in the pathogenesis of AD was followed by computational approaches. Methods: This study invloved 30 patients with LOAD and 30 non-demented controls. The relative expression of T-cell cytokines (IFN-γ, TNF-α, IL-4, and IL-5) and transcription factors (T-bet and GATA-3) were assessed using real-time PCR. Additionally, protein-protein interaction (PPI) was investigated by gene network construction. Results: A significant decrease at T-bet, IFN-γ, TNF-α, and GATA-3 mRNA levels was detected in the LOAD group, compared to the controls. However, there was no significant difference in IL-4 or IL-5 mRNA levels. Network analysis revealed a list of the highly connected protein (hubs) related to mitogen-activated protein kinase (MAPK) signaling and Th17 cell differentiation pathways. Conclusion: The findings point to a molecular dysregulation in Th-related genes, which can promising in the early diagnosis or targeted interventions of AD. Furthermore, the PPI analysis showed that upstream off-target stimulation may involve MAPK cascade activation and Th17 axis induction.

scholarly journals The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Dong-Yu Fan ◽  
Hao-Lun Sun ◽  
Pu-Yang Sun ◽  
Jie-Ming Jian ◽  
Wei-Wei Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Fibrinogen ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
And Gender ◽  
T Tau ◽  
The Relationship ◽  
Phosphorylated Tau 181 ◽  
Normal Controls

Recent studies show that fibrinogen plays a role in the pathogenesis of Alzheimer’s disease (AD), which may be crucial to neurovascular damage and cognitive impairment. However, there are few clinical studies on the relationship between fibrinogen and AD. 59 11C-PiB-PET diagnosed AD patients and 76 age- and gender-matched cognitively normal controls were included to analyze the correlation between plasma β-amyloid (Aβ) and tau levels with fibrinogen levels. 35 AD patients and 76 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation between CSF Aβ and tau levels with fibrinogen levels. In AD patients, plasma fibrinogen levels were positively correlated with plasma Aβ40 and Aβ42 levels, and negatively correlated with CSF Aβ42 levels. Besides, fibrinogen levels were positively correlated with CSF total tau (t-tau), and phosphorylated tau-181 (p-tau) levels and positively correlated with the indicators of Aβ deposition in the brain, such as t-tau/Aβ42, p-tau/Aβ42 levels. In normal people, fibrinogen levels lack correlation with Aβ and tau levels in plasma and CSF. This study suggests that plasma fibrinogen levels are positively correlated with Aβ levels in the plasma and brain in AD patients. Fibrinogen may be involved in the pathogenesis of AD.

Sign in / Sign up

Export Citation Format

Share Document