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Table 1 CSF biomarkers to distinguish cases with ADD from cases with non-ADD

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 non-AD patients Number of control patients CSF biomarkers Optimal cut-off* Sensitivity % (95% CI)** Specificity % (95% CI)** AUC (95% CI) SL (p value)#
Shoji et al. [12] 55 68 34 42 158.6 fmol/mL
42/40 ratio## 0.078## 51 82 NP
Lewczuk et al. [13] 22 11 35 42 550 pg/mL 100 80 0.923
42/40 ratio 9.75 95.2 88.4 0.944 NP
Spies et al. [22] 69 69 47 AD vs controls
  16 DLB  42 93 87 0.949
  27 FTD  42/40 ratio 93 87 0.947 NP
  26 VaD   AD vs non-AD
   42 83 74 0.811 NP
42/40 ratio 85 85 0.903  
Hertze et al. [32] 94 166 (MCI)
29 (DD)
38 AD vs controls  
42 MSD < 523 73 89 0.88 (0.82–0.93)
42 MSD/40 ratio < 0.069 93 86 0.91 (0.86–0.95) NP
42 MSD/38 ratio < 0.37 87 82 0.89 (0.83–0.93) NP
MCI-AD vs MCI
42 MSD < 523 67 71 0.73 (0.66–0.80)
42 MSD/40 ratio < 0.069 85 71 0.86 (0.79–0.91) NP
42 MSD/38 ratio < 0.37 88 71 0.85 (0.79–0.91) NP
Gabelle et al. [14] 52 34 42 AD vs FTD
42 > 464 79 62 0.75
42/40 ratio ≤11.1 79 76 0.85 n.s.
42/38 ratio ≤2.00 88 86 0.87 n.s.
Slaets et al. [16] 80
69 (NP)
11 (AD+CVD)
75
24 DLB (15 NP)
29 FTD (12 NP)
22 VaD (11 NP)
30 42 517 pg/mL 81 59 0.747 (0.670–0.827)
42/40 ratio 0.057 81 60 0.749 (0.673–0.826) NP
Nutu et al. [17] 48 127
43 PD
33 PDD
       
51 DLB 107 AD vs control
42 444 ng/L 94 72 0.871 (0.811–0.930) -NP
42/40 ratio 0.125 92 79 0.871 (0.801–0.933)  
AD vs PDD
42 449 ng/L 94 61 0.805 (0.704–0.905)
42/40 ratio 0.150 90 81 0.910 (0.844–0.976) NP
AD vs DLB
42 387 ng/L 88 41 0.675 (0.570–0.780)
42/40 ratio 0.115 90 57 0.759 (0.664–0.853) NP
Baldeiras et al. [18]     AD vs controls
42 534 pg/mL 82 74 0.818
40/42 ratio 8.3 59 81 0.719 NP
AD vs FTD      
42 538 pg/mL 70 82 0.791
40/42 ratio 5.4 59 87 0.778 NP
Dumurgier et al. [19] 367 (AD+ non-AD) 0 AD vs non-AD
42 737–836 pg/mL 78 79 0.81
42/40 ratio 0.050–0.082 73 78 0.81 NP
Struyfs et al. [23] 100 50 50 AD vs controls
50 (AD) 17 (DLB)  42 < 722 pg/mL 98.0 74.0 0.874
50 (MCI-AD) 17 (FTD)  42/40 ratio < 0.1099 85.7 78.0 0.881 NP
  16 (VaD)  42/38 ratio < 0.269 81.6 82.0 0.858 NP
    AD vs non-AD
42 < 694 pg/mL 95.9 40.0 0.686
42/40 ratio < 0.1215 93.9 50.0 0.782 NP
42/38 ratio < 0.2730 81.6 68.0 0.804 NP
Bousiges et al. [25] 70 55 15 Pro-AD vs pro-DLB
31 (AD-d) 20 (DLB-d)  42 ≤ 730 ng/L 84.6 71.4 0.84 (0.74–0.92)
39 (pro-AD) 35 (pro-DLB)  42/40 ratio ≤ 0.0529 88.9 100 0.95 (0.83–0.99) NP
    AD-d vs DLB-d
42 ≤ 504 ng/L 67.7 80 0.77 (0.63–0.88)
42/40 ratio ≤ 0.0799 92.3 88.9 0.86 (0.64–0.97) NP
Janelidze et al. [24] Cohort 2 Cohort 2 Cohort 2 AD vs MCI
75 (AD) 62 (MCI) 53 42 0.817 (0.743–0.890)
35 (MCI-AD) 34 (VaD) Cohort 3 42/40 ratio 0.879 (0.823–0.936) < 0.028
Cohort 3 47 (DLB/PDD) 328 42/38 ratio 0.856 (0.790–0.923) < 0.222
137 33 (FTD)   AD vs DLB/PDD
  Cohort 3  42 0.583 (0.476–0.690)
  35 (DLB/PDD)  42/40 ratio 0.792 (0.707–0.877) < 0.001
  128 (PD)  42/38 ratio 0.796 (0.710–0.883) < 0.001
    AD vs VaD
42 0.698 (0.580–0.816)
42/40 ratio 0.880 (0.814–0.946) < 0.001
42/38 ratio 0.860 (0.786–0.935) < 0.001
AD vs non-AD  
42 0.720 (0.651–0.788)
42/40 ratio 0.863 (0.813–0.912) < 0.001
42/38 ratio 0.863 (0.813–0.913) < 0.001
Lehmann et al. [26] 342 562 0 AD vs non-AD
Cohort 1 Cohort 1   Cohort 1  
124 276  42 500 pg/mL 0.78 (0.734–0.818)
Cohort 2 Cohort 2  42/40 ratio 0.1 0.90 (0.865–0.926) < 0.0001
218 286   Cohort 2  
42 700 pg/mL 0.60 (0.553–0.641)
42/40 ratio 0.05 0.77 (0.728–0.803) < 0.0001
  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. ##Note that the ratio in the original article is inversed, but for consistency, the Aβ42/40 ratio has been calculated for this table. Amyloid beta, AD Alzheimer’s Disease, ADD AD dementia, Ad-d demented AD patients, AUC area under curve, CJD Creutzfeldt-Jakob Disease, CSF cerebrospinal fluid, DLB dementia with Lewy bodies, DLB-d demented DLB patients, FTD frontotemporal dementia, MCI mild cognitive impairment, MCI-AD MCI that subsequently developed ADD or MCI due to AD, NP neuropathologically confirmed, NP not provided, NPH normal pressure hydrocephalus, n.s not significant, PD Parkinson’s Disease, PDD Parkinson’s Disease dementia, pro-AD prodromal-AD patients, pro-DLB prodromal-DLB patients, PsD psychiatric disorders, SL significance level, VaD vascular dementia