TABLE 4.

Surrogate biomarkers of prion diseases.

Biomarker	Body fluid	Detection method	Sensitivity	Specificity	References
14-3-3	CSF	Western blotting, capture assay, ELISA	53%–100% (sCJD), 0%–97% (gCJD/FFI/GSS), 60%–75% (iCJD), 45%–58% (vCJD)	27%–100%	Hsich et al. (1996), Zerr et al. (1998, 2000a, b), Beaudry et al. (1999); Kenney et al. (2000), Lemstra et al. (2000); Aksamit et al. (2001), Green et al. (2001, 2002), Peoc’h et al. (2001); Otto et al. (2002), Geschwind et al. (2003); Van Everbroeck et al. (2003), Collins et al. (2006), Sanchez-Juan et al. (2006, 2007), Bahl et al. (2009), Gmitterová et al. (2009); Ladogana et al. (2009), Chohan et al. (2010); Stoeck et al. (2012), Sano et al. (2013); Schmitz et al. (2016), Hermann et al. (2018); Abu-Rumeileh et al. (2019), Llorens et al. (2020b)
tau	CSF	ELISA	75%–100% (sCJD), 0%–86% (gCJD/FFI/GSS), 53% (iCJD), 24%–80% (vCJD)	49%–100%	Otto et al. (1997, 2002), Green et al. (2001); Van Everbroeck et al. (2003), Sanchez-Juan et al. (2006, 2007), Bahl et al. (2009); Ladogana et al. (2009), Chohan et al. (2010); Hamlin et al. (2012), Stoeck et al. (2012); Sano et al. (2013), Steinacker et al. (2016), Abu-Rumeileh et al. (2018, 2019)
	Serum/Plasma	Simoa	57%–91% (sCJD/gCJD)	83%–97%	Steinacker et al. (2016), Thompson et al. (2018, 2020)
NSE	CSF	ELISA, TRACE	79%–85% (sCJD), 64% (gCJD), 52% (vCJD), 0% (GSS/FFI)	83%–92%	Zerr et al. (1995); Beaudry et al. (1999), Aksamit et al. (2001); Green et al. (2001), Bahl et al. (2009); Ladogana et al. (2009)
S100B	CSF	ELISA	65%–94% (sCJD), 87% (gCJD), 78% (vCJD), 50% (GSS), 20% (FFI)	76%–90%	Beaudry et al. (1999); Green et al. (2001), Ladogana et al. (2009); Chohan et al. (2010)
	Serum	ECL	78%–84% (sCJD/gCJD)	63%–81%	Otto et al. (1998); Steinacker et al. (2016)
α-Synuclein	CSF	ECL, ELISA	86%–98% (sCJD)	91%–98%	Llorens et al. (2017, 2018), Kruse et al. (2018); Schmitz et al. (2019)
NFL	CSF	ELISA	86%–97% (CJD/GSS)	43%–95%	Steinacker et al. (2016), Abu-Rumeileh et al. (2018, 2019)
	Serum/plasma	Simoa	93%–100% (sCJD/gCJD)	57%–100%	Steinacker et al. (2016), Thompson et al. (2018, 2020)

CJD, Creutzfeldt–Jakob disease; ECL, electrochemiluminescence-based assays; ELISA, enzyme-linked immunosorbent assay; FFI, fatal familial insomnia; gCJD, genetic Creutzfeldt–Jakob disease; GSS, Gerstmann–Sträussler–Scheinker syndrome; iCJD, iatrogenic Creutzfeldt–Jakob disease; NFL, neurofilament light chain protein; NSE, neuron-specific enolase; sCJD, sporadic Creutzfeldt–Jakob disease; Simoa, single molecule array; TRACE, time-resolved amplified cryptate emission; vCJD, variant Creutzfeldt–Jakob disease.