Alterations in Mitochondrial Dynamic-related Genes in the Peripheral Blood of Alzheimer’s Disease Patients

2020 ◽  
Vol 17 (7) ◽  
pp. 616-625
Author(s):  
Nattaporn Pakpian ◽  
Kamonrat Phopin ◽  
Kuntida Kitidee ◽  
Piyarat Govitrapong ◽  
Prapimpun Wongchitrat
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Performance ◽  
Peripheral Blood ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Pathological Feature ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Expression Levels

Background: Mitochondrial dysfunction is a pathological feature that manifests early in the brains of patients with Alzheimer’s Disease (AD). The disruption of mitochondrial dynamics contributes to mitochondrial morphological and functional impairments. Our previous study demonstrated that the expression of genes involved in amyloid beta generation was altered in the peripheral blood of AD patients. Objective: The aim of this study was to further investigate the relative levels of mitochondrial genes involved in mitochondrial dynamics, including mitochondrial fission and fusion, and mitophagy in peripheral blood samples from patients with AD compared to healthy controls. Methods: The mRNA levels were analyzed by real-time polymerase chain reaction. Gene expression profiles were assessed in relation to cognitive performance. Results: Significant changes were observed in the mRNA expression levels of fission-related genes; Fission1 (FIS1) levels in AD subjects were significantly higher than those in healthy controls, whereas Dynamin- related protein 1 (DRP1) expression was significantly lower in AD subjects. The levels of the mitophagy-related genes, PTEN-induced kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3), were significantly increased in AD subjects and elderly controls compared to healthy young controls. The mRNA levels of Parkin (PARK2) were significantly decreased in AD. Correlations were found between the expression levels of FIS1, DRP1 and PARK2 and cognitive performance scores. Conclusion: Alterations in mitochondrial dynamics in the blood may reflect impairments in mitochondrial functions in the central and peripheral tissues of AD patients. Mitochondrial fission, together with mitophagy gene profiles, might be potential considerations for the future development of blood-based biomarkers for AD.

CD33 mRNA Has Elevated Expression Levels in the Leukocytes of Peripheral Blood in Patients with Late-Onset Alzheimer’s Disease

Gerontology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Fatemeh Heidari ◽  
George Ansstas ◽  
Farzam Ajamian
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mrna Expression ◽  
Peripheral Blood ◽  
In Silico ◽  
Late Onset ◽  
Mrna Levels ◽  
Coding Region ◽  
Expression Levels ◽  
Functional Polymorphisms

<b><i>Background/Aims:</i></b> In despite of conflicting results among different ethnic groups, the rs3865444 of CD33 gene has previously been identified as a risk factor for late-onset Alzheimer’s disease (LOAD).This study was aimed to evaluate the association between rs3865444 SNP with LOAD occurrence, and to investigate whether CD33 mRNA expression will change in the leukocytes of peripheral blood in LOAD patients. <b><i>Methods:</i></b> The rs3865444 polymorphism was genotyped in 233 LOAD and 238 control subjects using the Tetra-ARMS-PCR method. CD33 mRNAs expression in leukocytes were assessed and analyzed using the real-time qPCR method. We used in silico approach to analyze potential effects imparted by rs3865444 polymorphism in LOAD pathogenesis. <b><i>Results:</i></b> Our results show a significant increase in CD33 mRNA expression levels in white blood cells of LOAD patients, however, the association between CD33 rs3865444 polymorphism and LOAD was found to be not significant. We also noticed that LOAD patients with the C/A genotype had higher CD33 mRNA levels in their peripheral blood than those of the control group. <b><i>Conclusions:</i></b> rs3865444, located upstream of the 5′CD33 coding region, might positively influence CD33 mRNAs expression in leukocytes of LOAD versus healthy people. This is likely to happen through interfering rs3865444 (C) with the functional activity of several other transcription factors given that rs3865444 is in linkage disequilibrium with other functional polymorphisms in this coding region according to an in silico study. We propose that CD33 mRNAs elevation in peripheral immune cells – as a potential biomarker in LOAD – is related to peripheral immune system impairment.

scholarly journals Mitochondrial Deficits With Neural and Social Damage in Early-Stage Alzheimer’s Disease Model Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Afzal Misrani ◽  
Sidra Tabassum ◽  
Qingwei Huo ◽  
Sumaiya Tabassum ◽  
Jinxiang Jiang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Neuronal Morphology ◽  
Therapeutic Interventions ◽  
Early Event ◽  
Mitochondrial Morphology

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is thought to be an early event in the onset and progression of AD; however, the precise underlying mechanisms remain unclear. In this study, we investigated mitochondrial proteins involved in organelle dynamics, morphology and energy production in the medial prefrontal cortex (mPFC) and hippocampus (HIPP) of young (1∼2 months), adult (4∼5 months) and aged (9∼10, 12∼18 months) APP/PS1 mice. We observed increased levels of mitochondrial fission protein, Drp1, and decreased levels of ATP synthase subunit, ATP5A, leading to abnormal mitochondrial morphology, increased oxidative stress, glial activation, apoptosis, and altered neuronal morphology as early as 4∼5 months of age in APP/PS1 mice. Electrophysiological recordings revealed abnormal miniature excitatory postsynaptic current in the mPFC together with a minor connectivity change between the mPFC and HIPP, correlating with social deficits. These results suggest that abnormal mitochondrial dynamics, which worsen with disease progression, could be a biomarker of early-stage AD. Therapeutic interventions that improve mitochondrial function thus represent a promising approach for slowing the progression or delaying the onset of AD.

scholarly journals Protective Effects of Anti-depressant Citalopram Against Abnormal APP Processing and Amyloid Beta-induced Mitochondrial Dynamics, Biogenesis, Mitophagy and Synaptic Toxicities in Alzheimer’s Disease

2021 ◽  
Author(s):  
Arubala P Reddy ◽  
Xiangling Yin ◽  
Neha Sawant ◽  
P Hemachandra Reddy
Keyword(s):  
Electron Microscopy ◽  
Alzheimer’S Disease ◽  
Transmission Electron Microscopy ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Protective Role ◽  
Mrna Levels ◽  
Ht22 Cells ◽  
Transmission Electron

Abstract The purpose of this study is to study the neuroprotective role of selective serotonin reuptake inhibitor (SSRI), citalopram against Alzheimer’s disease (ad). Multiple SSRIs, including citalopram are reported to treat patients with depression, anxiety, and ad. However, their protective cellular mechanisms have not been studied completely. In the current study, we investigated the protective role of citalopram against impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective mitophagy, and synaptic dysfunction in immortalized mouse primary hippocampal cells (HT22) expressing mutant APP (SWI/IND) mutations. Using quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed mutant full-length APP/C-terminal fragments and Aβ levels and mRNA and protein levels of mitochondrial dynamics, biogenesis, mitophagy, and synaptic genes in mAPP-HT22 cells and mAPP-HT22 cells treated with citalopram. Increased levels of mRNA levels of mitochondrial fission genes, decreased levels of fusion biogenesis, autophagy, mitophagy and synaptic genes were found in mAPP-HT22 cells relative to WT-HT22 cells. However, in mAPP-HT22 cells treated with citalopram compared to mAPP-HT22 cells, revealed reduced levels of the mitochondrial fission genes, increased fusion, biogenesis, autophagy, mitophagy, and synaptic genes. Our protein data agrees with mRNA levels. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in mAPP-HT22 cells; these were reversed in citalopram treated mAPP-HT22 cells. Cell survival rates were increased in citalopram treated mAPP-HT22 relative to citalopram-untreated mAPP-HT22. Further, mAPP and C-terminal fragments were also reduced in citalopram treated cells. These findings suggest that citalopram reduces mutant APP and Aβ and mitochondrial toxicities and may have a protective role of mutant APP and Aβ-induced injuries in patients with depression, anxiety, and ad.

The Expression of Decoy Receptor 3 in Peripheral Blood Monocytes of Rheumatoid Arthritis Patient

2013 ◽  
Vol 709 ◽  
pp. 848-851
Author(s):  
Ke Xin Sun ◽  
Chun Hui Li ◽  
Yan Li ◽  
Su Hong Guo ◽  
Yi Ju Hou
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Arthritis Patient ◽  
Peripheral Blood ◽  
Pathological Process ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Expression Levels ◽  
Decoy Receptor 3

To investigate DcR3 mRNA levels of peripheral blood monocytes in rheumatoid arthritis(RA)，and analyzes the correlation between the DcR3 Levels of Peripheral Blood and the Disease Activity in Rheumatoid Arthritis Patient. The expression levels of DcR3 mRNA in peripheral Blood monocytes of 82 RA patients and 53 healthy controls were detected by real-time polymerase chain reaction. The expression levels of DcR3 mRNA of active stage in RA patients were higher than that of remission stage in RA patients and healthy controls(P<0.05); The correlationships between DcR3 mRNA levels and active renal score (DAS28)show positive correlation. The expression levels of peripheral blood DcR3 does significant increase in RA active patients and it is closely related with the activity of the disease which suggesting that DcR3 migh involved in the pathological process.

scholarly journals Hippocampal LMNA Gene Expression is Increased in Late-Stage Alzheimer’s Disease

2019 ◽  
Vol 20 (4) ◽  
pp. 878 ◽  
Author(s):  
Iván Méndez-López ◽  
Idoia Blanco-Luquin ◽  
Javier Sánchez-Ruiz de Gordoa ◽  
Amaya Urdánoz-Casado ◽  
Miren Roldán ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Stage ◽  
Fold Increase ◽  
Transcript Level ◽  
P Value ◽  
Mrna Levels ◽  
Lmna Gene ◽  
Expression Levels ◽  
Human Hippocampus

Lamins are fibrillary proteins that are crucial in maintaining nuclear shape and function. Recently, B-type lamin dysfunction has been linked to tauopathies. However, the role of A-type lamin in neurodegeneration is still obscure. Here, we examined A-type and B-type lamin expression levels by RT-qPCR in Alzheimer’s disease (AD) patients and controls in the hippocampus, the core of tau pathology in the brain. LMNA, LMNB1, and LMNB2 genes showed moderate mRNA levels in the human hippocampus with highest expression for the LMNA gene. Moreover, LMNA mRNA levels were increased at the late stage of AD (1.8-fold increase; p-value < 0.05). In addition, a moderate positive correlation was found between age and LMNA mRNA levels (Pearson’s r = 0.581, p-value = 0.018) within the control hippocampal samples that was not present in the hippocampal samples affected by AD. A-type and B-type lamin genes are expressed in the human hippocampus at the transcript level. LMNA mRNA levels are up-regulated in the hippocampal tissue in late stages of AD. The effect of age on increasing LMNA expression levels in control samples seems to be disrupted by the development of AD pathology.

scholarly journals Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8− Positive (AT8+) Tau in Alzheimer’s Disease

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110194
Author(s):  
Audra York ◽  
Angela Everhart ◽  
Michael P. Vitek ◽  
Kirby W. Gottschalk ◽  
Carol A. Colton
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolic Pathways ◽  
Cell Types ◽  
Specific Protein ◽  
Specific Gene ◽  
Specific Cell ◽  
Mrna Levels ◽  
Double Labeling ◽  
Expression Levels

Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer’s disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 ( RSAD1) and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. APOE4 vs APOE3 genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals.

scholarly journals Exploring the mRNA expression level of RELN in peripheral blood of schizophrenia patients before and after antipsychotic treatment

2020 ◽  
Author(s):  
Jiajun Yin ◽  
Yana Lu ◽  
Shui Yu ◽  
Zhanzhan Dai ◽  
Fuquan Zhang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Peripheral Blood ◽  
Antipsychotic Treatment ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Quantitative Real Time Pcr ◽  
Expression Levels ◽  
Before And After ◽  
The Brain

Abstract Background: The Reelin (RELN) gene encodes the protein reelin, which is a large extracellular matrix glycoprotein that plays a key role in brain development. Additionally, this protein may be involved in memory formation, neurotransmission, and synaptic plasticity, which have been shown to be disrupted in schizophrenia (SCZ). A decreasing trend in the expression of RELN mRNA in the brain and peripheral blood of SCZ patients has been observed. There is a need to determine whether changes in RELN mRNA expression in SCZ patients are the result of long-term antipsychotic treatment rather than the etiological characteristics of schizophrenia. The expression levels of RELN mRNA in the peripheral blood of 48 healthy controls and 30 SCZ patients before and after 12-weeks of treatment were measured using quantitative real-time PCR.Results: The expression levels of RELN mRNA in the SCZ group were significantly lower than that of healthy controls; however, after 12-weeks of antipsychotic treatment, RELN mRNA levels were significantly increased in the SCZ group.Conclusion: The up-regulation of RELN mRNA expression was current in SCZ patients after antipsychotic treatment, suggesting that the changes in RELN mRNA expression were related to the effect of the antipsychotic treatment.

scholarly journals Investigation of miR-155 and miR-758 Expression Levels in Peripheral Blood of Alzheimer’s Disease Patients

Experimed ◽  
2018 ◽  
pp. 58-61
Author(s):  
Ebru Ozer ◽  
◽  
Gamze Guven ◽  
Ebba Lohmann ◽  
Cagri Gulec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Expression Levels
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