scholarly journals Label-free optical quantification of structural alterations in Alzheimer’s disease

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Moosung Lee ◽  
Eeksung Lee ◽  
JaeHwang Jung ◽  
Hyeonseung Yu ◽  
Kyoohyun Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Label Free ◽  
Structural Alterations

scholarly journals Label-free vibrational imaging of different Aβ plaque types in Alzheimer’s disease reveals sequential events in plaque development

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Dominik Röhr ◽  
Baayla D. C. Boon ◽  
Martin Schuler ◽  
Kristin Kremer ◽  
Jeroen J. M. Hoozemans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Raman Imaging ◽  
Label Free ◽  
Human Brain Tissue ◽  
Plaque Development ◽  
Β Sheets ◽  
Diffuse Plaques ◽  
Insight Into

AbstractThe neuropathology of Alzheimer’s disease (AD) is characterized by hyperphosphorylated tau neurofibrillary tangles (NFTs) and amyloid-beta (Aβ) plaques. Aβ plaques are hypothesized to follow a development sequence starting with diffuse plaques, which evolve into more compact plaques and finally mature into the classic cored plaque type. A better molecular understanding of Aβ pathology is crucial, as the role of Aβ plaques in AD pathogenesis is under debate. Here, we studied the deposition and fibrillation of Aβ in different plaque types with label-free infrared and Raman imaging. Fourier-transform infrared (FTIR) and Raman imaging was performed on native snap-frozen brain tissue sections from AD cases and non-demented control cases. Subsequently, the scanned tissue was stained against Aβ and annotated for the different plaque types by an AD neuropathology expert. In total, 160 plaques (68 diffuse, 32 compact, and 60 classic cored plaques) were imaged with FTIR and the results of selected plaques were verified with Raman imaging. In diffuse plaques, we detect evidence of short antiparallel β-sheets, suggesting the presence of Aβ oligomers. Aβ fibrillation significantly increases alongside the proposed plaque development sequence. In classic cored plaques, we spatially resolve cores containing predominantly large parallel β-sheets, indicating Aβ fibrils. Combining label-free vibrational imaging and immunohistochemistry on brain tissue samples of AD and non-demented cases provides novel insight into the spatial distribution of the Aβ conformations in different plaque types. This way, we reconstruct the development process of Aβ plaques in human brain tissue, provide insight into Aβ fibrillation in the brain, and support the plaque development hypothesis.

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.

Noninvasive label-free nanoplasmonic optical imaging for real-time monitoring of in vitro amyloid fibrogenesis

Nanoscale ◽  
2014 ◽  
Vol 6 (7) ◽  
pp. 3561-3565 ◽  
Author(s):  
Sung Sik Lee ◽  
Luke P. Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Optical Imaging ◽  
Real Time ◽  
Label Free ◽  
Real Time Monitoring ◽  
Pathological Mechanism

We utilize nanoplasmonic optical imaging as the noninvasive and label-free method in order to monitorin vitroamyloid fibrogenesis in real-time, which is considered as the primary pathological mechanism of Alzheimer's disease.

Induced conformational change on ferrocenyl-terminated alkyls and their application as transducers for label-free immunosensing of Alzheimer's disease biomarker

RSC Advances ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 2414-2421 ◽  
Author(s):  
Abdelmoneim Mars ◽  
Wicem Argoubi ◽  
Sami Ben Aoun ◽  
Noureddine Raouafi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Electron Transfer ◽  
Conformational Change ◽  
Conformational Changes ◽  
Rate Constants ◽  
Label Free ◽  
Alkyl Chains ◽  
Disease Biomarker

ApoE Alzheimer's disease biomarker can be sensitively detected by a label-free platform using flexible ferrocene-terminated alkyl chains. The immunorecognition triggers conformational changes, which improve the rate constants of electron-transfer.

scholarly journals Molecular Dynamics simulations of TREM2 variants R47H and R62H show structural alterations at key binding regions leading to possible implications for mechanisms in Alzheimer’s disease.

2019 ◽  
Author(s):  
Georgina Elizabeth Menzies ◽  
Rebecca Sims ◽  
Julie Williams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Outcome ◽  
Protein A ◽  
Large Change ◽  
Receptor Protein ◽  
Protein Coding ◽  
Structural Alterations ◽  
Dynamics Simulations

Abstract Background There is strong evidence supporting the association between Alzheimer’s disease (AD) and protein-coding variants, R47H and R62H in triggering receptor expressed on myeloid cells 2 (TREM2). The TREM2 protein is an immune receptor protein found in brain microglia. These two variants are in a similar position in the protein but cause a different functional outcome. A structural alteration caused by the variants could be having a large effect on the protein. A crystallised structure was used to investigate structural differences. Both variants were inserted into the protein structure and these were subjected to 300ns of molecular dynamic simulation (MD) in order to investigate the link between structural change and AD risk.Results Results suggest structural alterations in both variant models of TREM2 which could be causing the reduced functional outcome. A large change was noted in the R47H model in the complementarity-determining region two (CDR2) loop, a proposed binding site for ligands such as APOE, a smaller change was observed in the R62H model in this same loop. The overall structure remained stable, possibly accounting for the reduced, not missing, function of TREM2 in disease.Conclusions These differing levels of structural impact could explain the in vitro observed differences in TREM2-ligand binding when the mutations are present. Further studies to investigate this binding loop could help not only a better understanding of TREM2’s role in the onset of dementia but also possibly provide a target for therapeutics.

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