scholarly journals Label-free high-resolution proteomic analysis of cerebrospinal fluid in Alzheimer's disease

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S223-S224
Author(s):  
Sun Ah Park ◽  
Jin Myung Jung ◽  
Jun Sung Park ◽  
Jeong Ho Lee ◽  
Bumhee Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
High Resolution ◽  
Proteomic Analysis ◽  
Label Free

scholarly journals Network Analysis of a Membrane-Enriched Brain Proteome across Stages of Alzheimer’s Disease

Proteomes ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 30 ◽  
Author(s):  
Lenora Higginbotham ◽  
Eric Dammer ◽  
Duc Duong ◽  
Erica Modeste ◽  
Thomas Montine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Analysis ◽  
Proteomic Analysis ◽  
Expression Patterns ◽  
Label Free ◽  
Post Mortem Brain ◽  
Brain Proteome ◽  
Associated Proteins ◽  
Membrane Bound

Previous systems-based proteomic approaches have characterized alterations in protein co-expression networks of unfractionated asymptomatic (AsymAD) and symptomatic Alzheimer’s disease (AD) brains. However, it remains unclear how sample fractionation and sub-proteomic analysis influences the organization of these protein networks and their relationship to clinicopathological traits of disease. In this proof-of-concept study, we performed a systems-based sub-proteomic analysis of membrane-enriched post-mortem brain samples from pathology-free control, AsymAD, and AD brains (n = 6 per group). Label-free mass spectrometry based on peptide ion intensity was used to quantify the 18 membrane-enriched fractions. Differential expression and weighted protein co-expression network analysis (WPCNA) were then used to identify and characterize modules of co-expressed proteins most significantly altered between the groups. We identified a total of 27 modules of co-expressed membrane-associated proteins. In contrast to the unfractionated proteome, these networks did not map strongly to cell-type specific markers. Instead, these modules were principally organized by their associations with a wide variety of membrane-bound compartments and organelles. Of these, the mitochondrion was associated with the greatest number of modules, followed by modules linked to the cell surface compartment. In addition, we resolved networks with strong associations to the endoplasmic reticulum, Golgi apparatus, and other membrane-bound organelles. A total of 14 of the 27 modules demonstrated significant correlations with clinical and pathological AD phenotypes. These results revealed that the proteins within individual compartments feature a heterogeneous array of AD-associated expression patterns, particularly during the preclinical stages of disease. In conclusion, this systems-based analysis of the membrane-associated AsymAD brain proteome yielded a unique network organization highly linked to cellular compartmentalization. Further study of this membrane-associated proteome may reveal novel insight into the complex pathways governing the earliest stages of disease.

scholarly journals High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer’s Disease in Human Cerebrospinal Fluid

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135365 ◽  
Author(s):  
Ronald C. Hendrickson ◽  
Anita Y. H. Lee ◽  
Qinghua Song ◽  
Andy Liaw ◽  
Matt Wiener ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
High Resolution ◽  
Disease Progression ◽  
Human Cerebrospinal Fluid ◽  
Progression Markers

Pilot proteomic analysis of cerebrospinal fluid in Alzheimer's disease

2021 ◽  
pp. 2000072
Author(s):  
Justin McKetney ◽  
Daniel J. Panyard ◽  
Sterling C. Johnson ◽  
Cynthia Carlsson ◽  
Corinne D. Engelman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Proteomic Analysis

scholarly journals Proteomic Profiling of Extracellular Vesicles Derived from Cerebrospinal Fluid of Alzheimer’s Disease Patients: A Pilot Study

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1959 ◽  
Author(s):  
Satoshi Muraoka ◽  
Mark P. Jedrychowski ◽  
Kiran Yanamandra ◽  
Seiko Ikezu ◽  
Steven P. Gygi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Extracellular Vesicles ◽  
Protein Composition ◽  
Amyloid Plaque ◽  
Label Free ◽  
Proteomic Profiling ◽  
Proteomics Analysis ◽  
And Control

Pathological hallmarks of Alzheimer’s disease (AD) are deposits of amyloid beta (Aβ) and hyper-phosphorylated tau aggregates in brain plaques. Recent studies have highlighted the importance of Aβ and tau-containing extracellular vesicles (EVs) in AD. We therefore examined EVs separated from cerebrospinal fluid (CSF) of AD, mild cognitive impairment (MCI), and control (CTRL) patient samples to profile the protein composition of CSF EV. EV fractions were separated from AD (n = 13), MCI (n = 10), and CTRL (n = 10) CSF samples using MagCapture Exosome Isolation kit. The CSF-derived EV proteins were identified and quantified by label-free and tandem mass tag (TMT)-labeled mass spectrometry. Label-free proteomics analysis identified 2546 proteins that were significantly enriched for extracellular exosome ontology by Gene Ontology analysis. Canonical Pathway Analysis revealed glia-related signaling. Quantitative proteomics analysis, moreover, showed that EVs expressed 1284 unique proteins in AD, MCI and CTRL groups. Statistical analysis identified three proteins—HSPA1A, NPEPPS, and PTGFRN—involved in AD progression. In addition, the PTGFRN showed a moderate correlation with amyloid plaque (rho = 0.404, p = 0.027) and tangle scores (rho = 0.500, p = 0.005) in AD, MCI and CTRL. Based on the CSF EV proteomics, these data indicate that three proteins, HSPA1A, NPEPPS and PTGFRN, may be used to monitor the progression of MCI to AD.

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