Table 2. Abnormal phosphorylation status... | Rockefeller University Press

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	0.67^ns	0.98**** [0.94–1.00]	0.99**** [0.97–1.00]	0.98**** [0.95–1.00]	0.95**** [0.89–1.00]	0.58^ns
Correlation, Spearman r
CSF vs. plasma: all	34	0.23^ns	0.78**** [0.59–0.88]	0.78**** [0.59–0.89]	0.68**** [0.43–0.83]	0.68**** [0.44–0.83]	−0.05^ns
CSF vs. plasma: Aβ⁺	15	0.29^ns	0.71** [0.31–0.89]	0.39^ns [−0.16–0.76]	0.54* [0.02–0.82]	0.19^ns	0.04^ns
Percent difference relative to controls^a
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	0.59^ns [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	0.61^ns [0.45–0.77]	0.86**** [0.73–0.99]	0.86****[0.74–0.99]	0.66^ns	0.67^ns
Aβ⁻ vs. Aβ⁺ CDR0.5	11 vs. 24	0.50^ns [0.30–0.71]	0.95**** [0.87–1.00]	0.93****[0.85–1.00]	0.86*** [0.74–0.98]	0.68^ns
Correlation, Spearman r
CSF vs. plasma: all	92	0.03^ns	0.79**** [0.70–0.86]	0.70**** [0.57–0.79]	0.45**** [0.27–0.60]	0.21^ns [−0.01 to 0.41]
CSF vs. plasma: Aβ+	50	0.03^ns	0.59**** [0.36–0.75]	0.25^ns	0.22^ns	0.08^ns
Aβ PET vs. plasma: all	66	−0.02^ns [−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	−0.20^ns [−0.51 to 0.16]	0.38* [0.04–0.64]	0.30^ns [−0.05–0.59]	0.25^ns [−0.12–0.55]	−0.04^ns [−0.39 to 0.32]

	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	0.67^ns	0.98**** [0.94–1.00]	0.99**** [0.97–1.00]	0.98**** [0.95–1.00]	0.95**** [0.89–1.00]	0.58^ns
Correlation, Spearman r
CSF vs. plasma: all	34	0.23^ns	0.78**** [0.59–0.88]	0.78**** [0.59–0.89]	0.68**** [0.43–0.83]	0.68**** [0.44–0.83]	−0.05^ns
CSF vs. plasma: Aβ⁺	15	0.29^ns	0.71** [0.31–0.89]	0.39^ns [−0.16–0.76]	0.54* [0.02–0.82]	0.19^ns	0.04^ns
Percent difference relative to controls^a
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	0.59^ns [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	0.61^ns [0.45–0.77]	0.86**** [0.73–0.99]	0.86****[0.74–0.99]	0.66^ns	0.67^ns
Aβ⁻ vs. Aβ⁺ CDR0.5	11 vs. 24	0.50^ns [0.30–0.71]	0.95**** [0.87–1.00]	0.93****[0.85–1.00]	0.86*** [0.74–0.98]	0.68^ns
Correlation, Spearman r
CSF vs. plasma: all	92	0.03^ns	0.79**** [0.70–0.86]	0.70**** [0.57–0.79]	0.45**** [0.27–0.60]	0.21^ns [−0.01 to 0.41]
CSF vs. plasma: Aβ+	50	0.03^ns	0.59**** [0.36–0.75]	0.25^ns	0.22^ns	0.08^ns
Aβ PET vs. plasma: all	66	−0.02^ns [−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	−0.20^ns [−0.51 to 0.16]	0.38* [0.04–0.64]	0.30^ns [−0.05–0.59]	0.25^ns [−0.12–0.55]	−0.04^ns [−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.

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