Searching for Reliable Premortem Protein Biomarkers for Prion Diseases

Progress and Challenges to Date

Di Ma; Lingjun Li

Expert Rev Proteomics. 2012;9(3):267-280.

Abstract and Introduction

Abstract

Prion diseases are a unique family of fatal neurodegenerative diseases caused by abnormal folding of normal cellular prion proteins in the brain. Due to the high risk of prion disease transmission and the lack of effective treatment to cure or delay the disease progression, prion diseases pose a serious threat to public health. To control and prevent prion diseases, an early diagnosis is urgently needed. Proteomic analysis has emerged as a powerful technology to decipher biological and pathophysiological processes and identify protein biomarkers indicative of disease. In this article, the authors review the use of the latest proteomic technologies for the identification of promising prion disease biomarkers, the challenges that exist in biomarker development pipelines and the new directions for utilizing proteomics for future biomarker discovery in the context of prion disease diagnostics.

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Table 1. Potential biomarkers of prion diseases identified by mass spectrometry-based proteomics.
Protein	Source of sample	Identification method	Prion disease	Ref.
14-3-3 protein	CSF	2D-GE	CJD	[119]
α1-antichymotrypsin	CSF	2D-GE	CJD	[50]
Apolipoprotein A1	CSF	2D-GE	CJD	[50]
Apolipoprotein A4	CSF	2D-GE	CJD	[50]
Apolipoprotein J	CSF	2D-GE	CJD	[50]
Apoliprotein E	CSF	2D-GE	CJD	[120]
Complement factor B/3a	CSF	2D-GE	CJD	[50]
Cystatin C	CSF	2D-GE, SELDI-TOF	CJD	[50,52]
Fatty acid binding protein	CSF, plasma	2D-GE	CJD	[56]
Fibrin-β	CSF	2D-GE	CJD	[50]
Fibrinogen γ chain	CSF	2D-GE	CJD	[50]
Gelsolin	CSF	2D-GE, 2D-DIGE	CJD	[50,51]
Hp2-α haptoglobin	CSF	2D-GE	CJD	[50]
Lactate dehydrogenase B chain	CSF	2D-DIGE	CJD	[51]
Neuron-specific enolase	CSF	2D-DIGE	CJD	[51]
Prostaglandin D2 synthase	CSF	2D-DE	CJD	[50]
Transferrin	CSF	2D-DE	CJD	[50]
Transthyretin	CSF, serum	2D-DIGE, SELDI-TOF	CJD, scrapie	[51,68]
Thymosin-β 4	CSF	MALDI-TOF	CJD	[53]
Ubiquitin	CSF	2D-GE, MALDI-TOF, SELDI-TOF	CJD	[50,53,121]
Serum amyloid P-component	Plasma	2D LC-MS/MS	Scrapie	[65]
Clusterin E/M	Urine	2D-DIGE	BSE	[75,78]
Ig γ-2 chain C region	Urine	2D-DIGE	BSE	[75]
Cystatin	Urine	2D-DIGE	BSE	[75]
Cathelicidin antimicrobial peptide	Urine	2D-DIGE	BSE	[75]
Uroguanylin	Urine	2-DIGE	BSE	[75]

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