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High-Sensitivity Single Molecule Array Assays for Pathological Isoforms in Parkinson's Disease.

Maia Norman1,2,3, Tal Gilboa1,2,4, David R Walt1,2,4

  • 1Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Clinical Chemistry
|January 22, 2022
PubMed
Summary

New assays detect low-concentration biomarkers for Parkinson's disease (PD). These measurements improve diagnostic accuracy, aiding clinical trial monitoring for neurodegenerative diseases.

Keywords:
Parkinson diseasepost-translational modificationssingle molecule arrays

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Area of Science:

  • Biomarker discovery
  • Neurodegenerative disease research
  • Assay development

Background:

  • Clinical trials for neurodegenerative diseases require sensitive detection of post-translational modifications (PTMs) and pathological isoforms.
  • Current immunoassays lack the sensitivity to detect these biomarkers at femtomolar concentrations.
  • There is a need for highly sensitive and validated assays for these critical markers.

Purpose of the Study:

  • To develop and validate a novel panel of single molecule array assays.
  • To measure specific pathological isoforms and PTMs relevant to Parkinson's disease (PD).
  • To assess the utility of these assays in distinguishing PD patients from healthy controls.

Main Methods:

  • Development of a single molecule array assay panel.
  • Validation using cerebrospinal fluid from 100 PD patients and 100 healthy controls.
  • Analysis of biomarkers including alpha synuclein, pSer129 alpha synuclein, DJ-1, C-reactive protein, p396 tau, and neurofilament light chain.

Main Results:

  • Alpha synuclein, pSer129 alpha synuclein, DJ-1, and C-reactive protein were reduced in PD patients.
  • p396 tau and neurofilament light chain were increased in PD patients.
  • A random forest model using the panel achieved an area under the curve of 0.70.

Conclusions:

  • Measurement of PTMs and pathological isoforms enhanced diagnostic accuracy in PD.
  • These novel assays show potential for monitoring patient response in clinical trials.
  • Sensitive detection of biomarkers is crucial for advancing neurodegenerative disease therapeutics.