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Updated: Dec 23, 2025

Highly Sensitive and Quantitative Detection of Proteins and Their Isoforms by Capillary Isoelectric Focusing Method
07:58

Highly Sensitive and Quantitative Detection of Proteins and Their Isoforms by Capillary Isoelectric Focusing Method

Published on: September 19, 2018

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Isoelectric point region pI≈7.4 as a treasure island of abnormal proteoforms in blood

Mohammad Pirmoradian1,2, Dag Aarsland3, Roman A Zubarev1

  • 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Discoveries (Craiova, Romania)
|April 21, 2020
PubMed

Insights

Abnormal protein forms (proteoforms) associated with neurodegenerative diseases are concentrated near pH 7.4. This finding offers a new approach for detecting Alzheimer's disease biomarkers.

Area of Science:

  • Biochemistry
  • Proteomics
  • Neuroscience

Background:

  • Human blood protein distribution shows a minimum around pH 7.4.
  • Normal proteins avoid this pH to prevent precipitation.
  • Abnormal proteoforms, disease indicators, can exist across the entire pH spectrum.

Purpose of the Study:

  • To test the hypothesis that disease-associated proteoforms are detectable around pH 7.4.
  • To investigate the potential of the pH 7.4 region as a biomarker discovery site for neurodegenerative diseases.

Main Methods:

  • Blood serum from Alzheimer's disease patients was analyzed.
  • Capillary isoelectric focusing separated proteins by isoelectric point (pI).
  • Liquid chromatography-tandem mass spectrometry identified and quantified proteoforms.

Main Results:

  • Proteoforms in the pI 7.4±0.1 region were significantly higher in patients with fast memory decline.
  • This specific pI region showed greater differences between patient groups than other regions.
  • Absolute separation of fast and slow decliner samples was achieved based on proteoforms at pI≈7.4.

Conclusions:

  • The pI≈7.4 region acts as a "treasure island" for abnormal proteoforms.
  • This finding supports the detection of neurodegenerative disease biomarkers.
  • The study highlights a promising avenue for developing diagnostic tools for various diseases.

Keywords:
Alzheimer's diseaseIsoelectric pointbiomarkersproteoforms

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