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Updated: Aug 10, 2025
06:34
A Tailored HPLC Purification Protocol That Yields High-purity Amyloid Beta 42 and Amyloid Beta 40 Peptides, Capable of Oligomer Formation
Published on: March 27, 2017
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Post-Translational Chemical Modification of Amyloid-β Peptides by 4-Hydroxy-2-Nonenal
Hiroyuki Kikuchi1,2, Miki Takahashi1,3, Hiroaki Komatsu1
1Department of Pharmacology, 1009C Stellar Chance Laboratories, University of Pennsylvania, Philadelphia, PA, USA.
Journal of Alzheimer'S Disease : JAD
|February 13, 2023
Summary
Formic acid disaggregates amyloid-β (Aβ) fibrils but causes artifacts and cannot disaggregate HNE-modified Aβ. This limits quantification of pathological HNE-Aβ in brain tissue.
Area of Science:
- Neuroscience
- Biochemistry
- Analytical Chemistry
Background:
- Formic acid (FA) is used to extract amyloid-β (Aβ) peptides from brain tissue.
- The effect of FA on post-translationally modified Aβ, especially 4-hydroxy-2-nonenal (HNE)-modified Aβ, is unclear.
- HNE accelerates Aβ aggregation and is found near amyloid plaques.
Purpose of the Study:
- To assess formic acid's ability to disaggregate HNE-modified Aβ peptides.
- To determine if FA induces covalent modifications in Aβ during disaggregation.
Main Methods:
- Quantitative liquid chromatography-tandem mass spectrometry was employed.
- Monomeric Aβ peptides and their covalently modified forms were analyzed.
Main Results:
- FA disaggregated standard Aβ fibrils.
- FA induced time-dependent formylation and methionine oxidation in Aβ.
- FA failed to disaggregate HNE-modified Aβ peptides.
Conclusions:
- Formic acid treatment introduces artifacts and cannot disaggregate HNE-modified Aβ.
- Current FA-based methods may underestimate the pathological burden of HNE-Aβ in brain tissue.
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