TABLE 4.
Blood-derived biomarker panels for prediction of cerebrospinal fluid (CSF) and PET status as gold standards.
| Overlapped biomarkers |
Panel | AUC | Reference standard | Subjects (N) and disease stage | Subjects characteristics (n, mean ± SD) | References | |||||||
| Aβ42 | Aβ42/Aβ40 | APOEε4 | APOE | CgA | EOT3 | NF-L | pTau181 | ||||||
| ■ | ■ | Aβ42/Aβ40, APOEε4 status | 0.88–0.913a | Aβ-PET |
N = 176 HC, MCI, AD |
Month 18 n = 176, avg. age: 73.7 ± 7.2, f/m: 86/90 Month 36 n = 169, avg. age: 75 ± 7.1, f/m: 83/86 Month 54 n = 135, avg. age: 76.9 ± 7.1, f/m: 65/70 |
Doecke et al., 2020 | ||||||
| ■ | ■ | Aβ42/Aβ40, APOEε4 status | 0.83 (95% CI 0.77–0.89; Sn = 76%; Sp = 75%)a | CSF Aβ,Aβ-PET |
N = 248 SCD |
N = 248, avg. age: 61 ± 9, f/m: 103/145 | Verberk et al., 2018 | ||||||
| ■ | ■ | Aβ42/Aβ40, APOEε4 status | 0.78 | Aβ-PET |
N = 95 SMC, non-SMC |
Aβ−
n = 63, avg. age: 77.65 ± 5.62, f/m: 44/19 Aβ+ n = 32, avg. age: 79.50 ± 5.32, f/m: 19/13 |
Chatterjee et al., 2019 | ||||||
| ■ | ■ | Aβ42/Aβ40, APOEε4 status | 0.519 (APOEε4+) 0.648 (APOEε4−) |
Aβ-PET |
N = 117 APOEε4+, APOEε4− |
APOEε4+
n = 28, avg. age: 71.6 ± 11.2, f/m: 18/10 APOEε4− n = 89, avg. age: 71.7 ± 12.2, f/m: 50/39 |
Tateno et al., 2017 | ||||||
| ■ | ■ | ■ | Aβ42/Aβ40, APOEε4 status, tau, NF-L | Cohort 1: 0.80–0.87; Cohort 2: 0.86 | CSF Aβ42/Aβ40 |
N = 1079 CU, MCI, AD |
Cohort 1 N = 842, avg. age: 72 ± 5.6, f/m: 446/396 Cohort 2 n = 237, avg. age: 66 ± 10, f/m: 120/117 |
Palmqvist et al., 2019 | |||||
| ■ | ■ | Aβ42/Aβ40, GFAP, NF-L | Total: 0.88 (Sn = 0.82, Sp = 0.86) Non-demented: 0.84 (Sn = 0.70, Sp = 0.86) |
Aβ-PET |
N = 252 SCD, MCI, AD |
PET+
n = 176, avg. age: 63 ± 7 years, f/m: 87/89 PET− n = 76, avg. age: 61 ± 9 years, f/m: 27/49 |
Verberk et al., 2020 | ||||||
| ■ | ■ | Aβ42/Aβ40, pTau181 | 0.84 (95% CI = 0.79–0.89) | Amyloid PET, Tau PET, CSF P-tau181 | Cohort 1: N = 182 Cohort 2: N = 344 Preclinical AD, MCI, AD |
Cohort 1
N = 182, avg. age: 72, f/m: 79/103 Cohort 2 n = 344, avg. age: 71, f/m: 174/170 |
Janelidze et al., 2020 | ||||||
| ■ | ■ | ■ | ■ | Aβ42, CgA, EOT3, APOEε4 status | 0.84 (Sn = 0.82; Sp = 0.62; PPV = 0.81; NPV = 0.64) | CSF Aβ42 |
N = 358 HC, MCI, AD |
HC
n = 58, avg. age: 75.11 ± 0.77, f/m: 28/30 MCI n = 198, avg. age: 74.37 ± 7.49, f/m: 65/133 AD n = 102, avg. age: 74.86 ± 7.88, f/m: 43/59 |
Eke et al., 2020 | ||||
| ■ | ■ | ■ | ■ | ■ | Aβ42, APOE, CgA, EOT3, APOEε4 status | 0.84 (Sn = 0.78, Sp = 0.73) | CSF Aβ42, tTau, and pTau181 |
N = 566 HC, MCI, AD |
Validation: MCI n = 198, avg. age: 75.13 ± 7.32, f/m: 75/123 AD n = 10, avg. age: 73.73 ± 10.04, f/m: 4/6 |
Goudey et al., 2017 | |||
| ■ | ■ | Brain derive dexosomal Aβ42, pTau181, T-tau | discovery cohort: 0.86–0.97; validation cohort: 0.85–0.98 | CFS Aβ42, T-tau, and P-T181-tau |
N = 298 HC, aMCI, AD |
N = 298, avg. age: 65 ± 6, f/m: 162/136 | Jia et al., 2019 | ||||||
Aβ42, amyloid-β42; Aβ42/Aβ40, amyloid-β 42-40 ratio; APOE, apolipoprotein; T-tau, total tau; pTau181, phosphorylated tau 181; CgA, chromogranin-A; EOT3, eotaxin 3; AUC, area under the curve; CI, confidence interval; CSF, cerebrospinal fluid; AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment; SCD, subjective cognitive decline.
aAge, gender, and presence of APOEε4 allele were included as covariates. The black squares show the overlapping biomarkers from the different studies.