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Table 1 Summary of studies on candidate CSF biomarkers for VaD, VCI and SSVD according to their discrimination power (vs. Controls and/or AD)

From: Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report

Candidate biomarker Study [Ref] Date Change HC n NC n VaD n VCI n SSVD n AD n Difference vs. Controls Difference vs. AD Sn/Sp vs. Controls Sn/Sp vs. AD
Albumin ratio (CSF/serum) Wallin et al. [30] 1990 30 - 53 - - - P < 0.001 - - -
Bjerke et al [72] 2009 52 - - - 9 20 NS NS - -
Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.005 P < 0.01 - -
Wallin et al. [32] 2001 18 - - - 25 - P < 0.001 - - -
NSE Blennow et al. [41] 1994 33 - 19 - - 45 P < 0.0001 NS - -
TNF-α Tarkowski et al. [55] 1999 25 - 33 - - 34 P < 0.001 - - -
VEGF Tarkowski et al. [56] 2002 27 - 26 - - 20 P = 0.03 NS - -
TGF-beta Tarkowski et al. [56] 2002 27 - 26 - - 20 P < 0.0004 NS - -
YKL-40 Olsson et al. [59] 2013 - 65 19 - - - P < 0.05 - - -
MMP-9 Adair et al. [62] 2004 8 - 15 - - 30 P < 0.003 P < 0.0001 - -
Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.05 P < 0.05 - -
MMP-10 Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.005 NS - -
MMP-2 Bjerke et al. [33] 2011 30 - - - 26 30 NS NS - -
MMP-3 Bjerke et al. [33] 2011 30 - - - 26 30 NS NS - -
TIMP-1 Ohrfelt et al. [57] 2011 52 - - - 7 15 P = 0.01 - - -
Ohrfelt et al. [57] 2011 52 - - - 8 24 P = 0.03 - - -
Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.05 P < 0.005 - -
TIMP-2 Bjerke et al. [33] 2011 30 - - - 26 30 NS NS - -
NF-L Wallin et al. [32] 2001 18 - - - 25 - P < 0.001 - Sn 68% Sp 85% -
Bjerke et al. [72] 2009 52 - - - 9 20 P < 0.001 NS - -
Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.0001 P < 0.05 - -
MBP Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.0001 P < 0.005 - -
Sulfatide Fredman et al. [85] 1992 19 - 20 - - 43 P < 0.0001 P < 0.0001 - -
Total tau (τT) Wallin et al. [32] 2001 18 - - - 25 - NS - Sn 85% Sp 36% -
Paraskevas et al. [103] 2009 68 _- 23 -_ -_ 92 P < 0.05 P < 0.05 -_ Sn 80% Sp 86%
Bjerke et al. [72] 2009 52 - - - 9 20 NS P < 0.005 - -
Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.005 NS - -
Phospho-tau (τp-181) Paraskevas et al. [103] 2009 68 -_ 23 _- -_ 92 NS P < 0.01 -_ Sn 84% Sp79%
Bjerke et al. [72] 2009 52 - - - 9 20 NS P < 0.005 - -
Bjerke et al. [33] 2011 30 - - - 26 30 NS P < 0.05 - -
42 Paraskevas et al. [103] 2009 68 _- 23 -_ _- 92 NS NS -_ Sn 73% Sp 70%
Bjerke et al. [72] 2009 52 - - - 9 20 P < 0.05 P < 0.005 - -
Bjerke et al. [33] 2011 30 - - - 26 30 P < 0.001 NS - -
42, τT, τp-181 (combination) Paraskevas et al. [103] 2009 68 -_ 23 -_ _- 92 NS P < 0.01 _- Sn 87% Sp 89%
sAPPβ Bjerke et al. [77] 2014         Correlation with WML - - -
  1. VaD Vascular Dementia, VCI Vascular Cognitive Impairment, SSVD Subcortical Small Vessel Disease, AD Alzheimer’s disease, HC Healthy Controls, NC Neurological Controls, Sn/Sp Sensitivity/Specificity, n number of controls/patients, reduced levels, ↑ increased levels, → no difference vs. controls, − not included, NS Not Significant