Table 1 Characteristics of the included studies in the systematic review and meta-analysis

Simren et al. [16]

2020

318

Cross-sectional

C: 46/53

MCI: 51/65

AD: 40/63

C: 29.07 ± 1.26

MCI: 27.21 ± 1.82

AD: 21.07 ± 4.42

C: 73 ± 6.14

MCI: 74.47 ± 5.89

AD: 76.35 ± 5.76

C: 11.23 ± 4.8

MCI: 8.97 ± 4.28

AD: 7.82 ± 3.66

C: 31/99 (31.3%)

MCI: 39/107 (36.4%)

AD: 58/103 (56.3%)

Plasma NFL level is increased in AD and MCI groups compared to healthy controls. NFL could be a diagnostic factor due to AD and MCI group changes

Gerards et al. [17]

2022

111

Cross-sectional

MCI: 33/24

AD: 24/30

MCI: 27 ± 2.1

AD: 23 ± 3.6

MCI: 69.1 ± 9.7

AD: 74.3 ± 8.2

C: NM

MCI: 13 ± 3

AD: 12 ± 2

NM

Measuring plasma NFL using SIMOA could be a diagnostic factor in AD and MCI groups

Gleerup et al. [18]

2021

115

Cross-sectional

C: 11/6

MCI: 25/22

AD: 22/29

C: 28.9 ± 0.8

MCI: 26.8 ± 3.2

AD: 22.9 ± 4.3

C: 68.4 ± 8.3

MCI: 71.1 ± 8.2

AD: 72.7 ± 7.5

NM

NM

There is no correlation between the level of saliva NFL and plasma NFL measured by SIMOA in AD, MCI, and healthy control groups

Lewczuk et al. [19]

2018

110

Cross-sectional

C: 22/19

MCI: 10/25

AD: 13/21

C: 29.3 ± 0.9

MCI: 26.7 ± 2.1

AD: 21.2 ± 3.4

C: 52.5 ± 13.1

MCI: 71.3 ± 8.4

AD: 70.8 ± 7.6

NM

NM

Plasma NFL is increased in AD compared to the control group, and plasma NFL could be used as a screening biomarker between groups with cognitively declined function

Lin et al. [20]

2018

234

Cross-sectional

C: 31/28

MCI: 27/29

AD: 56/63

C: 27.8 ± 2.1

MCI: 26.4 ± 2.3

AD: 18.6 ± 6.2

C: 77.0 ± 6.2

MCI: 77.3 ± 5.1

AD: 76.0 ± 5.6

C: 12.4 ± 5.0

MCI: 9.5 ± 4.8

AD: 11.0 ± 3.7

C: 7/59 (12.1%)

MCI: 13/56 (23.2%)

AD: 42/119 (35.3%)

Plasma NFL may be a potential biomarker in diagnosing AD; NFL is also associated with cognitive status and cognitive function

Sugarman et al. [21]

2020

579

Cross-sectional

C: 89/149

MCI: 77/108

AD: 88/68

C: 29.39 ± 0.91

MCI: 28.20 ± 1.67

AD: 21.11 ± 6.17

C: 72.38 ± 7.69

MCI: 74.99 ± 7.24

AD: 76.74 ± 8.12

C: 16.56 ± 2.54

MCI: 15.51 ± 2.74

AD: 14.95 ± 2.95

C: 77/235 (32.8%)

MCI: 59/181 (32.6%)

AD: 88/153 (57.5%)

Plasma NFL is a potential biomarker in diagnosing AD and is also very sensitive to cognitive status and decline

Zhou et al. [22]

2017

578

Cross-sectional

C: 106/87

MCI: 133/65

AD: 97/90

C: 29.1 ± 0.99

MCI: 26.9 ± 1.8

AD: 23.3 ± 2.1

C: 75.7 ± 4.9

MCI: 74.5 ± 7.4

AD: 75.5 ± 7.4

C: 16.0 ± 2.8

MCI: 15.8 ± 3.0

AD: 14.7 ± 3.1

NM

Plasma NFL is not an accurate biomarker for diagnosing the early stages of AD

Hall et al. [23]

2021

546

Cross-sectional

C: 87/328

MCI: 35/63

AD: 15/18

C: 26.97 ± 2.59

MCI: 23.92 ± 3.65

AD: 16.98 ± 5.87

59.22 ± 6.97

65.61 ± 8.47

73.727 ± 8.80

C: 8.353 ± 4.30

MCI: 6.370 ± 3.99

AD: 4.818 ± 4.67

NM

Plasma NFL could be an early diagnostic factor in differentiating MCI and healthy controls in the Mexican–American population

Wu et al. [24]

2021

428

Cross-sectional (participants recruited from 2 cohorts)

C: 45/76

MCI: 68/80

AD: 68/91

C: 29.16 ± 1.12

MCI: 26.33 ± 2.24

AD: 16.66 ± 6.73

C: 69.3 ± 7.1

MCI: 69.7 ± 8.8

AD: 66.9 ± 9.9

C: 11.1 ± 3.8

MCI: 11.0 ± 3.9

AD: 8.5 ± 4.4

C: 13/121 (10.7%)

MCI: 58/148 (39.2%)

AD: 82/159 (51.6%)

The level of plasma NFL is a reliable diagnostic factor in AD patients in the Chinese population

Shim et al. [25]

2022

99

Cross-sectional

MCI: 6/31

AD: 17/45

MCI: 21.86 ± 3.61

AD: 14.94 ± 5.51

MCI: 77.14 ± 6.09

AD: 79.39 ± 6.66

C: NM

MCI: 7.46 ± 4.93

AD: 5.92 ± 4.76

C: NM

MCI: 11/34 (32.4%)

AD: 13/46 (28.3%)

Plasma NFL level could be used as a possible biomarker in diagnosing AD, and the NFL level is also associated with cognitive decline

Mattsson et al. [6]

2017

570

Prospective Case–control

C: 106/87

MCI: 132/65

AD: 94/86

C: 29.1 ± 1

MCI: 26.9 ± 1.8

AD: 23.2 ± 2.1

C: 75.9 ± 4.9

MCI: 74.7 ± 7.5

AD: 75.3 ± 7.3

C: 16.0 ± 2.9

MCI: 15.8 ± 3.0

AD: 14.7 ± 3.1

C: 50/193 (25.9%)

MCI: 103/197 (52.3%)

AD: 123/180 (68.3%)

Plasma NFL level is elevated in AD patients as compared to the control group. Hence, plasma NFL is correlated with cognitive decline, and plasma NFL is an accurate biomarker in diagnosing AD

Parvizi et al. [26]

2022

167

Cross-sectional

C: 20/24

MCI: 34/29

AD: 24/36

C: NM

MCI: 26.66 ± 2.27

AD: 19 ± 6.83

C: 62.16 ± 10.49

MCI:69 ± 14.03

AD: 69.36 ± 12,53

NM

NM

Plasma NFL is a predictive factor in diagnosing AD

Wang et al. [27]

2022

Cohort 1: 40

Cohort

C: 11/9

AD: 8/12

C: 28.83 ± 1.59

AD: 15.25 ± 6.98

C: 56.58 ± 4.98

AD: 56.58 ± 4.18

C: 10 ± 2.39

AD: 9.08 ± 0.59

C: 1/20 (5%)

AD: 6/30 (30%)

Plasma NFL changes was significant in AD compared to healthy controls

Wang et al. [27]

2022

Cohort 2: 40

Cohort

C: 9/11

MCI: 7/13

C: 28.5 ± 2.39

MCI: 25.41 ± 2.59

C: 56.91 ± 8.17

MCI: 62.41 ± 11.36

C: 9.25 ± 5.38

MCI: 9.66 ± 3.19

C: 2/20 (12%)

MCI: 7/20 (44%)

MCI group had a higher plasma NFL concentration compared to healthy controls

Frank et al. [28]

2022

569

Cross-sectional

C: 87/148

MCI: 86/67

AD: 76/105

C: 29.39 ± 0.91

MCI: 28.20 ± 1.68

AD: 21.12 ± 6.21

C: 72.38 ± 7.69

MCI: 74.96 ± 7.25

AD: 76.82 ± 8.13

C: 16.56 ± 2.54

C: 15.52 ± 2.77

AD: 14.95 ± 2.95

C: 77/235 (33%)

MCI: 60/181 (33%)

AD: 89/153 (58%)

In AD diagnosis, elevated plasma NFL concentration was correlated with a higher conditional odds ratio. In contrast, NFL concentration was not associated with an MCI diagnosis

Asken et al. [29]

2022

Cohort1: 50

Cross-sectional

NM

NM

NM

NM

NM

Plasma NFL concentration in MCI was lower compared to control group

Asken et al. [29]

2022

Cohort2: 71

Cross-sectional

NM

NM

NM

NM

NM

AD patients had lower level of NFL compared to MCI patients