Table 5 Diagnostic performance of the CSF NfL and α-syn RT-QuIC assays in the differential diagnosis of patients with PD and PD-CI vs APD, MSA and PSP/CBS

From: Head-to-head comparison of four cerebrospinal fluid and three plasma neurofilament light chain assays in Parkinsonism

Diagnostic group

Biomarker

NfL cut off, pg/ml

+/−

Sensitivity (%) 95% CI

Specificity (%) 95% CI

Accuracy (%)95% CI

PD

α-syn RT-QuIC

-

194/22

89.8

-

-

PD-CI

α-syn RT-QuIC

-

55/1

98.2

-

-

MSA

α-syn RT-QuIC

-

3/124

-

97.6

-

PSP/CBS

α-syn RT-QuIC

-

2/112

-

98.2

-

APD

α-syn RT-QuIC

-

5/236

-

97.9

-

PD vs APD

CSF NfLELISA + α-syn RT-QuIC

< 700

212/4 vs 8/232

98.2 (95.3–99.5)

96.7 (93.5–98.5)

97.4 (94.5–98.6)

 

CSF NfLCLEIA + α-syn RT-QuIC

< 700

212/4 vs 13/225

98.2 (95.3–99.5)

94.5 (90.8–97.1)

96.3 (94.1–97.8)

 

CSF NfLSIMOA + α-syn RT-QuIC

< 650

205/1 vs 10/225

99.5 (97.3–99.9)

95.7 (92.3–97.9)

97.5 (95.6-98.8)

 

CSF NfLELLA + α-syn RT-QuIC

< 750

210/6 vs 5/232

97.2 (94.0-98.9)

97.9 (95.2–99.3)

97.6 (95.7–98.8)

PD-CI vs APD

CSF NfLELISA + α-syn RT-QuIC

< 700

53/1 vs 8/232

98.2 (90.1–99.9)

96.7 (93.5–98.5)

96.9 (94.3-98.6)

 

CSF NfLCLEIA + α-syn RT-QuIC

< 700

53/1 vs 13/225

98.2 (90.1–99.9)

94.5 (90.8–97.1)

95.2 (92.1–97.4)

 

CSF NfLSIMOA + α-syn RT-QuIC

< 650

53/1 vs 10/225

98.2 (90.1–99.9)

95.7 (90.1–99.9)

95.7 (92.3–97.9)

 

CSF NfLELLA + α-syn RT-QuIC

< 750

52/1 vs 5/232

98.1 (89.9-99.9)

97.9 (95.2–99.3)

97.9 (95.6–99.2)

PD vs MSA

CSF NfLELISA + α-syn RT-QuIC

< 700

212/4 vs 1/126

98.2 (95.3–99.5)

99.2 (95.7–99.9)

98.5 (96.6-99.5)

 

CSF NfLCLEIA + α-syn RT-QuIC

< 700

212/4 vs 1/126

98.2 (95.3–99.5)

99.2 (95.7–99.9)

98.5 (96.6–99.5)

 

CSF NfLSIMOA + α-syn RT-QuIC

< 650

205/1 vs 1/124

99.5 (97.3–99.9)

99.2 (95.6–99.9)

99.4 (97.8–99.9)

 

CSF NfLELLA + α-syn RT-QuIC

< 750

210/6 vs 1/124

97.2 (94.0–98.9)

99.2 (95.6–99.9)

97.9 (95.8–99.2)

PD-CI vs MSA

CSF NfLELISA + α-syn RT-QuIC

< 700

53/1 vs 1/126

98.2 (90.1–99.9)

99.2 (95.7–99.9)

98.9 (96.1–99.9)

 

CSF NfLCLEIA + α-syn RT-QuIC

< 700

53/1 vs 1/126

98.2 (90.1–99.9)

99.2 (95.7–99.9)

98.9 (96.1–99.9)

 

CSF NfLSIMOA + α-syn RT-QuIC

< 650

53/1 vs 1/124

98.2 (90.1–99.9)

99.2 (95.6–99.9)

98.9 (96.0–99.9)

 

CSF NfLELLA + α-syn RT-QuIC

< 750

52/1 vs 1/124

98.1 (89.9–99.9)

99.2 (95.6–99.9)

98.9 (96.0–99.9)

PD vs PSP/CBS

CSF NfLELISA + α-syn RT-QuIC

< 700

212/4 vs 7/106

98.2 (95.3–99.5)

93.8 (87.7–97.5)

96.7 (94.1–98.3)

 

CSF NfLCLEIA + α-syn RT-QuIC

< 700

212/4 vs 7/105

98.2 (95.3–99.5)

93.8 (87.6–97.5)

96.7 (94.1–98.3)

 

CSF NfLSIMOA + α-syn RT-QuIC

< 650

205/1 vs 9/101

99.5 (97.3–99.9)

91.8 (85.0–96.2)

96.8 (94.3–98.5)

 

CSF NfLELLA + α-syn RT-QuIC

< 750

210/6 vs 4/108

97.2 (94.0–98.9)

96.4 (91.1–99.0)

96.9 (94.5–98.5)

PD-CI vs PSP/CBS

CSF NfLELISA + α-syn RT-QuIC

< 600

53/1 vs 3/110

98.2 (90.1–99.9)

97.4 (92.4–99.5)

97.6 (93.9–99.3)

 

CSF NfLCLEIA + α-syn RT-QuIC

< 600

53/1 vs 2/110

98.2 (90.1–99.9)

98.2 (93.7–99.8)

98.2 (94.8–99.6)

 

CSF NfLSIMOA + α-syn RT-QuIC

< 550

53/1 vs 6/104

98.2 (90.1–99.9)

94.6 (88.5–97.9)

95.7 (91.4–98.3)

 

CSF NfLELLA + α-syn RT-QuIC

< 650

52/1 vs 1/111

98.1 (89.9–99.9)

99.1 (95.1–99.9)

98.8 (95.7–99.9)

  1. APD atypical parkinsonian disorder, α-syn RT-QuIC α-synuclein real-time quaking-induced conversion, CI confidence interval, CSF cerebrospinal fluid, MSA multiple system atrophy, PD Parkinson’s disease, PSP/CBS progressive supranuclear palsy/corticobasal syndrome, PD-CI PD-cognitively impaired, SAA seed amplification assay, +/− positive/negative