Table 2. Abnormal phosphorylation status detected in AD CSF tau (Aβ+) is recapitulated in plasma tau.
n | t-tau | pT217/T217 | p-tau-217 level | pT181/T181 | p-tau-181 level | pS202/S202 | |
---|---|---|---|---|---|---|---|
Tau SILK discovery cohort | |||||||
AUROC | |||||||
CSF Aβ− vs. Aβ+ | 19 vs. 15 | 0.95**** [0.88–1.00] | 1.00**** [1.00–1.00] | 1.00**** [1.00–1.00] | 0.95**** [0.89–1.00] | 0.98**** [0.95–1.00] | 0.72* [0.55–0.90] |
Plasma Aβ− vs. Aβ+ | 19 vs. 15 | 0.67ns | 0.98**** [0.94–1.00] | 0.99**** [0.97–1.00] | 0.98**** [0.95–1.00] | 0.95**** [0.89–1.00] | 0.58ns |
Correlation, Spearman r | |||||||
CSF vs. plasma: all | 34 | 0.23ns | 0.78**** [0.59–0.88] | 0.78**** [0.59–0.89] | 0.68**** [0.43–0.83] | 0.68**** [0.44–0.83] | −0.05ns |
CSF vs. plasma: Aβ+ | 15 | 0.29ns | 0.71** [0.31–0.89] | 0.39ns [−0.16–0.76] | 0.54* [0.02–0.82] | 0.19ns | 0.04ns |
Percent difference relative to controlsa | |||||||
CSF | |||||||
All Aβ+ vs. controls | 15 vs. 17 | 188 (110)ns | 215 (31)ns | 791 (110)**** | 25 (18)**** | 252 (110) | −14 (57)**** |
Aβ+/CDR = 0 vs. controls | 5 vs. 17 | 112 (90)ns | 167 (27)ns | 450 (84)*** | 19 (19)* | 154 (97) | −6 (59)* |
Aβ+/CDR = 0.5 vs. controls | 8 vs. 17 | 146 (83)ns | 235 (30)ns | 683 (71)**** | 30 (18)**** | 213 (79) | −19 (57)**** |
Plasma | |||||||
All Aβ+ vs. controls | 15 vs. 17 | 29 (58)**** | 342 (68)**** | 506 (95)**** | 74 (39)** | 128 (80) | −4 (55)**** |
Aβ+/CDR = 0 vs. controls | 5 vs. 17 | 20 (53)ns | 228 (56)** | 285 (56)*** | 60 (43)ns | 86 (58) | −5 (55)ns |
Aβ+/CDR = 0.5 vs. controls | 8 vs. 17 | 29 (61)ns | 282 (73)**** | 379 (93)**** | 78 (36)ns | 136 (85) | −4 (54)** |
CSF/plasma ratio | |||||||
All cohort | 34 | 102 (31) | 4.1 (1.2) | 418 (197) | 1.6 (0.5) | 160 (62) | 0.5 (0.2) |
Aβ− | 19 | 99 (22) | 4.6 (1.2) | 435 (101) | 1.8 (0.5) | 178 (57) | 0.6 (0.3) |
Aβ+ | 15 | 106 (39) | 3.6 (1.3) | 396 (272) | 1.3 (0.2) | 136 (60) | 0.5 (0.2) |
Aβ SILK validation cohort | |||||||
AUROC | |||||||
CSF | |||||||
All Aβ− vs. Aβ+ | 42 vs. 50 | 0.78**** [0.68–0.88] | 1.00**** [0.99–1.00] | 0.96**** [0.92–1.00] | 0.97**** [0.93–1.00] | 0.87**** [0.80–0.95] | |
Aβ− vs. Aβ+ CDR0 | 31 vs. 19 | 0.74** [0.59–0.89] | 0.99**** [0.98–1.00] | 0.96**** [0.92–1.00] | 0.92**** [0.81–1.00] | 0.82*** [0.68–0.95] | |
Aβ− vs. Aβ+ CDR0.5 | 11 vs. 22 | 0.74** [0.59–0.89] | 1.00**** [1.00–1.00] | 0.99**** [0.97–1.00] | 1.00**** [1.00–1.00] | 0.95*** [0.89–1.00] | |
Plasma | |||||||
Plasma Aβ− vs. Aβ+ | 42 vs. 50 | 0.59ns [0.47–0.71] | 0.92**** [0.87–0.98] | 0.93**** [0.87–0.98] | 0.75**** [0.65–0.86] | 0.72*** [0.61–0.82] | |
Aβ− vs. Aβ+ CDR0 | 31 vs. 20 | 0.61ns [0.45–0.77] | 0.86**** [0.73–0.99] | 0.86****[0.74–0.99] | 0.66ns | 0.67ns | |
Aβ− vs. Aβ+ CDR0.5 | 11 vs. 24 | 0.50ns [0.30–0.71] | 0.95**** [0.87–1.00] | 0.93****[0.85–1.00] | 0.86*** [0.74–0.98] | 0.68ns | |
Correlation, Spearman r | |||||||
CSF vs. plasma: all | 92 | 0.03ns | 0.79**** [0.70–0.86] | 0.70**** [0.57–0.79] | 0.45**** [0.27–0.60] | 0.21ns [−0.01 to 0.41] | |
CSF vs. plasma: Aβ+ | 50 | 0.03ns | 0.59**** [0.36–0.75] | 0.25ns | 0.22ns | 0.08ns | |
Aβ PET vs. plasma: all | 66 | −0.02ns [−0.26 to 0.23] | 0.70**** [0.54–0.81] | 0.67**** [0.51–0.79] | 0.45*** [0.22–0.63] | 0.26* [0.00–0.48] | |
Aβ PET vs. plasma: Aβ+ | 34 | −0.20ns [−0.51 to 0.16] | 0.38* [0.04–0.64] | 0.30ns [−0.05–0.59] | 0.25ns [−0.12–0.55] | −0.04ns [−0.39 to 0.32] |
Data are shown as mean (SD) for % of increase compared to control value and ratio and as value (95%, CI) for AUROC and Spearman r. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. ns, not significant per the Mann–Whitney test against aged and normal control groups (amyloid-negative participants without cognitive symptoms). Numbers in brackets indicate confidence intervals for AUROC.
Statistical significance (t test using the linear step-up procedure of Benjamini, Krieger, and Yekutieli) of the change compared to p-tau-181 level change as reference.