Proteomics Analysis of Blood Serums from Alzheimer’s Disease Patients Using iTRAQ Labeling Technology

2017 ◽  
Vol 56 (1) ◽  
pp. 361-378 ◽  
Author(s):  
Liming Shen ◽  
Liping Liao ◽  
Cheng Chen ◽  
Yi Guo ◽  
Dalin Song ◽  
...  
2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Chunyue Wang ◽  
Xueying Cai ◽  
Ruochen Wang ◽  
Siyu Zhai ◽  
Yongfeng Zhang ◽  
...  

Abstract Background Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer’s disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid β (Aβ)1–42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. Methods U251 cells were co-incubated with 10 μM of Aβ1-42 and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aβ1-42-damaged U251 cells. Results In Aβ1-42-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aβ, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis. Conclusions The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.


Author(s):  
David C. Hondius ◽  
Kristel N. Eigenhuis ◽  
Tjado H. J. Morrema ◽  
Roel C. van der Schors ◽  
Pim van Nierop ◽  
...  

2009 ◽  
Vol 8 (11) ◽  
pp. 5069-5079 ◽  
Author(s):  
Yair M. Gozal ◽  
Duc M. Duong ◽  
Marla Gearing ◽  
Dongmei Cheng ◽  
John J. Hanfelt ◽  
...  

2021 ◽  
Author(s):  
Guilherme Povala ◽  
Bruna Bellaver ◽  
Marco Antônio De Bastiani ◽  
Wagner S. Brum ◽  
Pamela C. L. Ferreira ◽  
...  

Abstract Background: Changes in soluble amyloid-beta (Aβ) levels in cerebrospinal fluid (CSF) are detectable at early preclinical stages of Alzheimer's disease (AD). However, whether Aβ levels can predict downstream AD pathological features in cognitively unimpaired (CU) individuals remains unclear. With this in mind, we aimed at investigating whether a combination of soluble Aβ isoforms can predict tau pathology (T+) and neurodegeneration (N+) positivity. Methods: We used CSF measurements of three soluble Aβ peptides (Aβ1‑38, Aβ1‑40 and Aβ1‑42) in CU individuals (n = 318) as input features in machine learning (ML) models aiming at predicting T+ and N+. Input data was used for building 2046 tuned predictive ML models with a nested cross-validation technique. Additionally, proteomics data was employed to investigate the functional enrichment of biological processes altered in T+ and N+ individuals. Results: Our findings indicate that Aβ isoforms can predict T+ and N+ with an area under the curve (AUC) of 0.929 and 0.936, respectively. Additionally, proteomics analysis identified 17 differentially expressed proteins (DEPs) in individuals wrongly classified by our ML algorithm. More specifically, enrichment analysis of gene ontology biological processes revealed an upregulation in myelinization and glucose metabolism-related processes in CU individuals wrongly predicted as T+. A significant enrichment of DEPs in pathways including biosynthesis of amino acids, glycolysis/gluconeogenesis, carbon metabolism, cell adhesion molecules and prion disease was also observed. Conclusions: Our results demonstrate that, by applying a refined ML analysis, a combination of Ab isoforms can predict T+ and N+ with a high AUC. CSF proteomics analysis highlighted a promising group of proteins that can be further explored for improving T+ and N+ prediction.


2006 ◽  
Vol 27 (7) ◽  
pp. 918-925 ◽  
Author(s):  
Rukhsana Sultana ◽  
Debra Boyd-Kimball ◽  
H. Fai Poon ◽  
Jain Cai ◽  
William M. Pierce ◽  
...  

2019 ◽  
Vol 16 (7) ◽  
pp. 613-621 ◽  
Author(s):  
Busra Gurel ◽  
Mehmet Cansev ◽  
Cansu Koc ◽  
Busra Ocalan ◽  
Aysen Cakir ◽  
...  

Background: CA1 subregion of the hippocampal formation is one of the primarily affected structures in AD, yet not much is known about proteome alterations in the extracellular milieu of this region. Objective: In this study, we aimed to identify the protein expression alterations throughout the pre-pathological, progression and pathological stages of AD mouse model. Method: The CA1 region perfusates were collected by in-vivo intracerebral push-pull perfusion from transgenic 5XFAD mice and their non-transgenic littermates at 3, 6 and 12 wereβmonths of age. Morris water maze test and immunohistochemistry staining of A performed to determine the stages of the disease in this mouse model. The protein expression differences were analyzed by label-free shotgun proteomics analysis. Results: A total of 251, 213 and 238 proteins were identified in samples obtained from CA1 regions of mice at 3, 6 and 12 months of age, respectively. Of these, 68, 41 and 33 proteins showed statistical significance. Pathway analysis based on the unique and common proteins within the groups revealed that several pathways are dysregulated during different stages of AD. The alterations in glucose and lipid metabolisms respectively in pre-pathologic and progression stages of the disease, lead to imbalances in ROS production via diminished SOD level and impairment of neuronal integrity. Conclusion: We conclude that CA1 region-specific proteomic analysis of hippocampal degeneration may be useful in identifying the earliest as well as progressional changes that are associated with Alzheimer’s disease.


2007 ◽  
Vol 1 (5) ◽  
pp. 506-512 ◽  
Author(s):  
Pao-Chi Liao ◽  
Lung Yu ◽  
Chih-Chieh Kuo ◽  
Chingju Lin ◽  
Yu-Min Kuo

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