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Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Detection of Amyloid Beta (Aβ) Oligomeric Composition Using Matrix-Assisted Laser Desorption Ionization Mass
Jasmine S-H Wang1,2,3, Shawn N Whitehead3, Ken K-C Yeung4,5
1Department of Chemistry, University of Western Ontario, London, ON, N6A 5B7, Canada.
Abstract:
The use of MALDI MS as a fast and direct method to detect the Aβ oligomers of different masses is examined in this paper. Experimental results suggest that Aβ oligomers are ionized and detected as singly charged ions, and thus, the resulting mass spectrum directly reports the oligomer size distribution. Validation experiments were performed to verify the MS data against artifacts. Mass spectra collected from modified Aβ peptides with different propensities for aggregation were compared. Generally, the relative intensities of multimers were higher from samples where oligomerization was expected to be more favorable, and vice versa. MALDI MS was also able to detect the differences in oligomeric composition before and after the incubation/oligomerization step. Such differences in sample composition were also independently confirmed with an in vitro Aβ toxicity study on primary rat cortical neurons. An additional validation was accomplished through removal of oligomers from the sample using molecular weight cutoff filters; the resulting MS data correctly reflected the removal at the expected cutoff points. The results collectively validated the ability of MALDI MS to assess the monomeric/multimeric composition of Aβ samples. Graphical Abstract ᅟ.
Insights
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) directly detects amyloid-beta (Aβ) oligomers by mass. This method accurately quanties Aβ oligomer size distribution and composition, validated through multiple experiments.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Neuroscience
Background:
- Amyloid-beta (Aβ) oligomers are implicated in neurodegenerative diseases.
- Accurate detection and characterization of Aβ oligomers are crucial for understanding disease mechanisms.
Purpose of the Study:
- To evaluate matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) as a method for detecting and quantifying Aβ oligomers.
- To validate the accuracy and reliability of MALDI MS for assessing Aβ sample composition.
Main Methods:
- MALDI MS was used to analyze Aβ peptides with varying aggregation propensities.
- Mass spectra were analyzed to determine oligomer size distribution.
- Validation included comparison with modified peptides, in vitro toxicity studies, and molecular weight cutoff filtration.
Main Results:
- MALDI MS directly detected Aβ oligomers as singly charged ions, with spectra reflecting oligomer size distribution.
- Higher multimer intensities correlated with increased aggregation propensity.
- MALDI MS accurately identified changes in Aβ composition before and after oligomerization.
- Filtration experiments confirmed the removal of specific oligomer sizes.
Conclusions:
- MALDI MS is a validated, fast, and direct method for assessing the monomeric/multimeric composition of Aβ samples.
- The technique provides reliable insights into Aβ oligomerization relevant to disease research.
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