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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 42 < 192 ng/L
419 (MCI)  42/40 ratio    NP
   Florbetapir PET > 1.11 SUV NP
Janelidze et al. [24] Cohort 1 Cohort 1 Cohort 1 Euroimmun
0 215 (MCI) 0 42 < 507.5 pg/mL 83.2 83.3 0.894 (0.850–0.937)
   42/40 ratio < 0.10 97.2 88.0 0.954 (0.923–0.986) 0.008
42/38 ratio < 0.29 92.5 88.9 0.943 (0.911–0.975) 0.007
MSD
42 < 495.9 pg/mL 85.0 88.9 0.916 (0.876–0.956)
42/40 ratio < 0.09 95.3 95.4 0.975 (0.952–0.998) < 0.001
42/38 ratio < 0.17 97.2 91.7 0.964 (0.935–0.992) 0.007
Quanterix
42 < 1742 pg/mL 73.3 77.5 0.810 (0.707–0.913)
42/40 ratio < 0.16 90.0 90.0 0.912 (0.834–0.991) 0.002
Lewczuk et al. [41] 0 199 CN & 0 42 735 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+)  42/40 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
42 ≤ 548 pg/mL 96 82 0.92 (0.89–0.95)
42/40 ratio ≤ 0.06 91 82 0.92 (0.88–0.95) NP
Modified Innotest
42 ≤ 1091 pg/mL 92 74 0.87 (0.83–0.91)
42/40 ratio ≤ 0.12 92 87 0.93 (0.90–0.96) ≤ 0.01
Euroimmun  
42 ≤ 449 pg/ 82 80 0.88
42/40 ratio mL
≤ 0.10
93 88 (0.84–0.92)
0.93 (0.90–0.96)
≤ 0.01
MSD
42 ≤ 506 pg/mL 94 76 0.89 (0.85–0.93)
42/40 ratio ≤ 0.08 96 89 0.95 (0.93–0.98) ≤ 0.001
Schindler et al. [46] 0 22 (MCI) 176 (CN) 42 < 1.098 pg/mL 0.85 (0.80–0.90)
  (~ 25% PiB+) (~ 25% PiB+) 42/40 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. 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