Competitive electrochemical immunosensor for the detection of unfolded p53 protein in blood as biomarker for Alzheimer's disease

Anal Chim Acta. 2020 Jan 6:1093:28-34. doi: 10.1016/j.aca.2019.09.042. Epub 2019 Sep 16.

Abstract

Alzheimer's disease is one of the most common causes of dementia nowadays, and its prevalence increases over time. Because of this and the difficulty of its diagnosis, accurate methods for the analysis of specific biomarkers for an early diagnosis of this disease are much needed. Recently, the levels of unfolded isoform of the multifunctional protein p53 in plasma have been proved to increase selectively in Alzheimer's Disease patients in comparison with healthy subjects, thus entering the list of biomarkers that can be used for the diagnosis of this illness. We present here the development of an electrochemical immunosensor based on nanostructured screen-printed carbon electrodes for the quantification of unfolded p53 in plasma samples. The sensor shows a suitable linear range (from 2 to 50 nM) for its application in real blood samples and a very low limit of detection (0.05 nM). The concentration of unfolded p53 has been accurately detected in plasma of elderly people in healthy conditions, subjects with mild cognitive impairment (MCI) and Alzheimer's Disease (AD) subjects, obtaining results with no significant differences to those provided by an ELISA assay. These results support the possibility of measuring unfolded p53 levels with a cheap, simple and miniaturized device with a promising future for point-of-care applications in the early diagnosis of Alzheimer's dementia.

Keywords: Alzheimer's disease; Electrochemical immunosensor; Gold nanoparticles; Screen-printed electrode; Unfolded p53; p53 protein.

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis*
  • Antibodies / immunology
  • Biomarkers / blood
  • Biosensing Techniques / methods*
  • Carbon / chemistry
  • Electrochemical Techniques / instrumentation
  • Electrochemical Techniques / methods
  • Electrodes
  • Gold / chemistry
  • Humans
  • Immunoassay / methods*
  • Intrinsically Disordered Proteins / blood*
  • Intrinsically Disordered Proteins / immunology
  • Limit of Detection
  • Metal Nanoparticles / chemistry
  • Protein Isoforms / blood
  • Protein Isoforms / immunology
  • Reproducibility of Results
  • Tumor Suppressor Protein p53 / blood*
  • Tumor Suppressor Protein p53 / immunology

Substances

  • Antibodies
  • Biomarkers
  • Intrinsically Disordered Proteins
  • Protein Isoforms
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Carbon
  • Gold