Mass spectrometry: A platform for biomarker discovery and validation for Alzheimer's and Parkinson's diseases

J Neurochem. 2019 Nov;151(4):397-416. doi: 10.1111/jnc.14635. Epub 2019 Jan 31.

Abstract

Accurate, reliable, and objective biomarkers for Alzheimer's disease (AD), Parkinson's disease (PD), and related age-associated neurodegenerative disorders are urgently needed to assist in both diagnosis, particularly at early stages, and monitoring of disease progression. Technological advancements in protein detection platforms over the last few decades have resulted in a plethora of reported molecular biomarker candidates for both AD and PD; however, very few of these candidates are developed beyond the discovery phase of the biomarker development pipeline, a reflection of the current bottleneck within the field. In this review, the expanded use of selected reaction monitoring (SRM) targeted mass spectrometry will be discussed in detail as a platform for systematic verification of large panels of protein biomarker candidates prior to costly validation testing. We also advocate for the coupling of discovery-based proteomics with modern targeted MS-based approaches (e.g., SRM) within a single study in future workflows to expedite biomarker development and validation for AD and PD. It is our hope that improving the efficiency within the biomarker development process by use of an SRM pipeline may ultimately hasten the development of biomarkers that both decrease misdiagnosis of AD and PD and ultimately lead to detection at early stages of disease and objective assessment of disease progression. This article is part of the special issue "Proteomics".

Keywords: Alzheimer's disease; Parkinson's disease; biomarker; central nervous system; mass spectrometry; selected reaction monitoring.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism*
  • Biomarkers / metabolism
  • Humans
  • Mass Spectrometry / methods*
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / metabolism*
  • Proteomics / methods*
  • Sensitivity and Specificity

Substances

  • Biomarkers