Abnormal tryptophan metabolism in Alzheimer’s disease (ALZ): label-free spectroscopy suggests an alternative theory of ALZ causation

2020 ◽  
Author(s):  
Laura A. Sordillo ◽  
Peter P. Sordillo ◽  
Robert R. Alfano
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tryptophan Metabolism ◽  
Alternative Theory ◽  
Label Free

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 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

Evaluation of the Therapeutic Effect of Lycoramine on Alzheimer’s Disease in Mouse Model

2020 ◽  
Vol 27 ◽  
Author(s):  
Irem Kiris ◽  
Merve Karayel Basar ◽  
Betul Sahin ◽  
Busra Gurel ◽  
Julide Coskun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Protein Expression ◽  
Cognitive Decline ◽  
Therapeutic Potential ◽  
Label Free ◽  
Differential Protein Expression ◽  
Differential Protein ◽  
Late Stages

Background:: Alzheimer’s disease is one of the leading health problems characterized by the accumulation of Aβ and hyperphosphorylated tau that accounts for the senile plaque formations causing extensive cognitive decline. Many of the clinical diagnostics of Alzheimer’s disease were made in the late stages where the pathological changes had already progressed. Objective:: The objective of this study is to evaluate the promising therapeutic effects of the natural compound lycoramine. The literature reports lycoramine’s therapeutic potential in several studies. Other publications show its mechanism of action on the molecular level via label-free differential protein expression analysis. Method:: Lycoramine and galantamine, an FDA approved drug used in treatment of the mild to moderate AD, were administered to 12 month-old 5xFAD mice. Effects of the compounds were investigated by Morris water maze, immunohistochemistry and label-free differential protein expression analyses. Results:: Here we demonstrated the reversal of cognitive decline via behavioral testing and the clearance of Aβ plaques. Proteomics analysis provided in-depth information on the statistically significant protein perturbations in the cortex, hippocampus and cerebellum sections to hypothesize the possible clearance mechanisms of the plaque formation and the molecular mechanism of the reversal of the cognitive decline in a transgenic mouse model. Bioinformatics analyses showed altered molecular pathways that can be linked with the reversal of cognitive decline observed after lycoramine administration but not with galantamine. Conclusion:: Lycoramine shows therapeutic potential to halt and reverse cognitive decline at the late stages of disease progression, and holds great promise for the treatment of Alzheimer’s disease.

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