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Table 4 Studies, in which emerging cerebrospinal fluid (CSF) and blood biomarkers were evaluated, are enlisted. The detection methods of the different biomarkers are also described

From: Neuropathological hints from CSF and serum biomarkers in corticobasal syndrome (CBS): a systematic review

References

Subgroups

Other biomarkers, mean (*)

Methods

Borroni et al. [37]

 

CSF Tau Form Ratio (33 kDa/55 kDa) 0.997 (0.34); (0.815–1.180)

Western Blot

Magdalinou et al. [36]

 

CSF sAPPb 238 ng/ml (167–309)

CSF YKL-40 21.5 ng/L × 10^4 (17.3–25.8)

CSF MCP-1 531 ng/L (406–655)

CSF sAPPa 394 ng/ml (217–516)

MesoScale Discovery: sAPPb + MCP-1 + sAPPa

ELISA: YKL-40

Hall et al. [28]

 

CSF Neurogranin-EL 370.2 pg/ml [167.4–525.2]

CSF Neurogranin-UGOT 174 pg/ml [107.5- 285]

CSF BACE-1 1693 pg/ml [1052–2722.4]

CSF NfH 0.799 pg/ml [0.649–1.083]

ELISA: Nerugranin-El + Neurogranin-UGOT + BACE-1 + NfH

Aerts et al. [29]

 

CSF Lactate 1666 micromol/L [1437–1808]

CSF Total Proteins 488 mg/L (126)

CSF Ab42/T-Tau 2.28 [0.64–3.69]

CSF Ab42/P-Tau 12.9 (7.1)

CSF P-Tau/T-Tau 0.18 [0.13–0.2]

ELISA: Ab42 + T-Tau + P-Tau

Benvenutto et al. [33]

CBS-A+

CSF Ab42/Ab40 0.06 [0.04–0.07]

CSF P-Tau/Ab42 0.26 [0.19–0.38]

CSF T-Tau/Ab42 1.7 [1.16–2.49]

CSF Ab42/P-Tau 3.89 [2.67–5.21]

ELISA: Ab42 + Ab40 + T-Tau + P-Tau

CBS-A−

CSF Ab42/Ab40 0.14 [0.10–0.16]

CSF P-Tau/Ab42 0.05 [0.04–0.07]

CSF T-Tau/Ab42 0.33 [0.22–0.51]

CSF Ab42/P-Tau 21.12 [14.62–26.68]

Meeter et al. [24]

 

CSF P-Tau/T-Tau ratio 0.13 [0.11–0.16]

Fujirebio: P-Tau + T-Tau

Alcolea et al. [29]

 

CSF sAPPb 556.4 ng/ml (226.9)

CSF YKL-40 280.6 ng/ml (60.4)

CSF sAPPb/YKL-40 2.0 (0.8)

CSF NfL/sAPPb 4.3 (2.6)

ELISA: sAPPb + YKL-40 + NfL

Borroni et al. [26]

CBS

CSF T-Tau/Ab42 0.86 (1.03)

Fujirebio: T-Tau + Ab42

CBS nAD-like

CSF T-Tau/Ab42 0.43 (0.29)

CBS AD-like

CSF T-Tau/Ab42 2.60 (1.20)

SPECT- nAD-like

CSF T-Tau/Ab42 0.44 (0.46)

SPECT- AD-like

CSF T-Tau/Ab42 2.83 (1.10)

Luk et al. [35]

Cohort A

CSF 3R-Tau 25 pg/ml "5–27"

CSF 4R-Tau 30 pg/ml "20–60"

RD3 and RD4 monoclonal antibodies + immuno-PCR: 3R-Tau, 4R-Tau

Cohort B

CSF 3R-Tau 2 pg/ml "1–3"

CSF 4R-Tau 10 pg/ml "5–15"

Cohort C

CSF 3R-Tau 25 pg/ml "10–50"

CSF 4R-Tau 5 pg/ml "4–8"

Cohort D

CSF 3R-Tau 5 pg/ml "4–10"

CSF 4R-Tau 0 pg/ml "0"

All cohorts

CSF 3R-Tau 20 pg/ml "0–50"

CSF 4R-Tau 10 pg/ml "20–60"

Cohort A + D

CSF 4RTau/T-Tau 0.037 (0.011)

CSF 4R-Tau/P-Tau 0.168 (0,092)

Doss et al. [23]

CBS + PSP patients

CSF NMDAR Ab (IgA, IgM or IgG) positivity percentage 54.5%

CSF NMDAR mean titre 1:10

Recombinant Immunofluorescence Assays

Quadalti et al. [20]

CBS + PSP patients

blood NfL 26.6 pg/ml [19.4–40.8]

CSF Ab40 8304 pg/ml [5761–10664]

CSF Ab42/Ab40 0.86 [0.77–0.94]

a-syn RT-QuIC: no seeding activity

Quanterix: blood NfL

Fujirebio: Ab40 + Ab42

RT-QuIC: a-syn seeding activity

Rodriguez et al. [52]

CBS + PSP patients

CSF YKL-40 273.8 ng/ml (57.5)

CSF Progranulin 5.2 ng/ml (1.3)

Fujirebio: YKL-40

ELISA: Progranulin

Schulz et al. [30]

 

blood aSyn 6548.94 pg/ml (2623.41)

CSF pS129 aSyn 2.07 pg/ml (0.83)

blood NfL 51.59 pg/ml (33.80)

CSF NfH 1.14 ng/ml (0.82)

CSF UCHL-1 2063.21 pg/ml (517.12)

CSF GFAP 19687.24 pg/ml (5320.02)

blood GFAP 290.42 pg/ml (165.23)

CSF S100B 3.78 pg/ml (1.08)

blood S100B 0.09 pg/ml ( 0.05)

CSF sTREM2 7170.38 pg/ml (3313.50)

blood sTREM2 5837.98 pg/ml (4072.41)

CSF YKL-40 177,413.75 pg/ml (64,746)

blood YKL-40 46,912.94 pg/ml (23,763)

ELISA: aSyn + blood aSyn + NfH

ELISA: UCHL-1 + GFAP + blood GFAP

ELISA: S100 B + sTREM2 + YKL-40 + blood YKL-40

Quanterix: blood NfL

Di Stefano et al. [51]

CBS

N

Fujirebio: Ab42 + T-Tau + P-Tau

CBS AD+

CSF T-Tau/Ab42 2.49 (1.33)

CSF P-Tau181/Ab42 0.43 (0.25)

CBS AD−

CSF T-Tau/Ab42 0.59 (0.3)

CSF P-Tau181/Ab42 0.09 (0.04)

  1. CSF biomarkers were detected in cerebrospinal fluid, blood biomarkers were detected
  2. (*) data reported as: (x) = standard deviation (SD); [x–y] = Interquartile Range (IQR); (x–y) = 95% Confidence Interval (95% CI)
  3. CBS-A+ CBS with underlying amyloid pathology, CBS-A− CBS not associated with amyloid pathology
  4. sAPPb soluble Amyloid Precursor Protein b, YKL-40 Mammalian Chitinase-Like Protein-40, MCP-1 Monocyte Chemoattractant Protein-1, sAPPa soluble Amyloid Precursor Protein a, BACE-1 Beta-Secretase-1, NfH Neurofilament Heavy chains, 3R Tau 3 Repeats Tau, 4R Tau 4 Repeats Tau, NMDAR Ab Antibodies Anti-NMDA Receptors, RT-QuIC Real-Time Quacking Induced Conversion, UCHL-1 ubiquitin C-terminal hydrolase L1, GFAP Glial Fibrillary Acid Protein, S100B S100 calcium-binding protein B, sTREM2 triggering receptor expressed on myeloid cells 2, Ab42 Beta-Amyloid 42, T-Tau Total-Tau, P-Tau Phospho-Tau, NfL Neurofilament Light Chains, aSyn alpha-Synuclein