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Table 3 Studies comparing CSF biomarkers and Aβ-PET

From: Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease

Study

Number of AD patients

Number of MCI/ non-AD patients

Number of control patients

CSF biomarkers/ PET

Optimal cut-off*

Sensitivity% (95% CI)**

Specificity% (95% CI)**

AUC (95% CI)

SL (p value)#

Mattsson et al. [42]

121

68 (SCD)

161

Aβ42

< 192 ng/L

–

–

–

–

419 (MCI)

 

Aβ42/40 ratio

 

–

–

 

NP

  

Florbetapir PET

> 1.11 SUV

–

–

–

NP

Janelidze et al. [24]

Cohort 1

Cohort 1

Cohort 1

Euroimmun

0

215 (MCI)

0

Aβ42

< 507.5 pg/mL

83.2

83.3

0.894 (0.850–0.937)

–

   

Aβ42/40 ratio

< 0.10

97.2

88.0

0.954 (0.923–0.986)

0.008

Aβ42/38 ratio

< 0.29

92.5

88.9

0.943 (0.911–0.975)

0.007

MSD

Aβ42

< 495.9 pg/mL

85.0

88.9

0.916 (0.876–0.956)

–

Aβ42/40 ratio

< 0.09

95.3

95.4

0.975 (0.952–0.998)

< 0.001

Aβ42/38 ratio

< 0.17

97.2

91.7

0.964 (0.935–0.992)

0.007

Quanterix

Aβ42

< 1742 pg/mL

73.3

77.5

0.810 (0.707–0.913)

–

Aβ42/40 ratio

< 0.16

90.0

90.0

0.912 (0.834–0.991)

0.002

Lewczuk et al. [41]

0

199 CN &

0

Aβ42

735 pg/mL

81.6 (68.0–91.2)

72.7 (64.8–79.6)

0.814 (0.752–0.865)

–

 

abnormal (150 PET−/ 49 PET+)

 

Aβ42/40 ratio

0.05

95.9 (86.0–99.5)

88.0 (81.7–92.7)

0.936 (0.892–0.966)

< 0.001

Janelidze et al. [44]

0

262 (MCI/SCD)

0

Innotest

Aβ42

≤ 548 pg/mL

96

82

0.92 (0.89–0.95)

–

Aβ42/40 ratio

≤ 0.06

91

82

0.92 (0.88–0.95)

NP

Modified Innotest

Aβ42

≤ 1091 pg/mL

92

74

0.87 (0.83–0.91)

–

Aβ42/40 ratio

≤ 0.12

92

87

0.93 (0.90–0.96)

≤ 0.01

Euroimmun

 

Aβ42

≤ 449 pg/

82

80

0.88

–

Aβ42/40 ratio

mL

≤ 0.10

93

88

(0.84–0.92)

0.93 (0.90–0.96)

≤ 0.01

MSD

Aβ42

≤ 506 pg/mL

94

76

0.89 (0.85–0.93)

–

Aβ42/40 ratio

≤ 0.08

96

89

0.95 (0.93–0.98)

≤ 0.001

Schindler et al. [46]

0

22 (MCI)

176 (CN)

Aβ42

< 1.098 pg/mL

–

–

0.85 (0.80–0.90)

–

 

(~ 25% PiB+)

(~ 25% PiB+)

Aβ42/40 ratio

< 0.075

–

–

0.93 (0.89–0.96)

NP

  1. *Optimal cut-offs were created using different statistical approaches—please see original articles for details. **Sensitivity and specificity are a function of the cut-off, and the cut-offs were calculated in different ways, therefore they are not clearly comparable across different articles. #Significance levels (p values) of the AUC values are comparisons of the Aβ isoform ratios vs Aβ42 alone. Aβ amyloid beta, AD Alzheimer’s Disease, ADAS-cog Alzheimer’s Disease Assessment Scale-cognitive subscale, AUC area under curve, cen centiloid, CN cognitively normal, CU centiloid units, DLB dementia with Lewy bodies, FTD frontotemporal dementia, MCI mild cognitive impairment, MCI-AD MCI that subsequently developed AD dementia, MSD Meso Scale Discovery, NP not provided, n.s not significant, PD Parkinson’s Disease, PDD Parkinson’s Disease with dementia, PET, positron emission tomography, MS-RMP mass spectrometry-based candidate reference measurement procedure, PiB carbon-11 labelled thioflavin-T derivative, Pittsburgh compound B, SCD subjective cognitive decline, SL significance level, SUV standardized uptake value, VaD subcortical vascular dementia, vis visual
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Alzheimer's Research & Therapy

ISSN: 1758-9193