From: P-tau subgroups in AD relate to distinct amyloid production and synaptic integrity profiles
Protein (n) | Protein level per group: estimate ± SE | Differences between p-tau subgroups: mean ± SE | p-values of contrasts | |||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Controls (n = 98) | Subgroup 1: p-tau ≤ 56 pg/ml (total n = 94) | Subgroup 2: p-tau 57–96 pg/ml (total n = 147) | Subgroup 3: p-tau 97–159 pg/ml (total n = 89) | Subgroup 4: p-tau > 159 pg/ml (total n = 11) | Interaction with cognitive stage: p-value | 1 vs controls | 2 vs 1 | 3 vs 1 | 4 vs 1 | 3 vs 2 | 4 vs 2 | 4 vs 3 | 1 vs controls | 2 vs 1 | 3 vs 1 | 4 vs 1 | 3 vs 2 | 4 vs 2 | 4 vs 3 | |
Preclinical AD | ||||||||||||||||||||
BACE1 (n = 51) | 0.1 ± 0.09 | − 0.27 ± 0.19 | 1.23 ± 0.19 | 1.86 ± 0.29 | 3.14 ± 0.86 | 0.381 | − 0.37 ± 0.21 | 1.5 ± 0.27 | 2.13 ± 0.34 | 3.41 ± 0.89 | 0.64 ± 0.34 | 1.92 ± 0.88 | 1.28 ± 0.91 | 0.788 | 9.0E−07 | 2.2E−08 | 2.8E−03 | 0.755 | 0.481 | 0.975 |
Aβ40 (n = 51) | 0.17 ± 0.1 | − 0.39 ± 0.2 | 0.96 ± 0.21 | 1.38 ± 0.31 | 2.78 ± 0.94 | 0.831 | − 0.55 ± 0.22 | 1.35 ± 0.29 | 1.77 ± 0.37 | 3.17 ± 0.96 | 0.42 ± 0.37 | 1.82 ± 0.96 | 1.4 ± 0.99 | 0.267 | 1.0E−04 | 5.5E−05 | 2.3E−02 | 0.998 | 0.721 | 0.973 |
NfL (n=50) | 0.15 ± 0.09 | 0.37 ± 0.17 | 0.92 ± 0.17 | 2.14 ± 0.26 | 2.05 ± 0.79 | 0.123 | 0.22 ± 0.19 | 0.56 ± 0.25 | 1.78 ± 0.31 | 1.69 ± 0.81 | 1.22 ± 0.31 | 1.13 ± 0.8 | − 0.09 ± 0.83 | 0.998 | 0.412 | 5.2E−07 | 0.549 | 2.3E−03 | 0.975 | 1.000 |
VAMP2 (n = 48) | 0.11 ± 0.1 | − 0.42 ± 0.21 | 1.09 ± 0.2 | 1.91 ± 0.3 | 2.96 ± 0.91 | 0.764 | − 0.53 ± 0.23 | 1.51 ± 0.29 | 2.32 ± 0.37 | 3.38 ± 0.93 | 0.81 ± 0.36 | 1.87 ± 0.93 | 1.06 ± 0.96 | 0.383 | 8.0E−06 | 1.5E−08 | 7.0E−03 | 0.414 | 0.620 | 0.999 |
NRGN (n = 51) | 0.09 ± 0.09 | 0.09 ± 0.17 | 1.65 ± 0.18 | 2.86 ± 0.26 | 3.96 ± 0.79 | 0.403 | 0 ± 0.19 | 1.56 ± 0.25 | 2.77 ± 0.31 | 3.87 ± 0.81 | 1.21 ± 0.32 | 2.31 ± 0.81 | 1.1 ± 0.84 | 1.000 | 1.3E−08 | 0.0E+00 | 5.7E−05 | 3.0E−03 | 0.094 | 0.988 |
Prodromal AD | ||||||||||||||||||||
BACE1 (n = 102) | 0.1 ± 0.09 | − 0.14 ± 0.15 | 0.62 ± 0.13 | 1.73 ± 0.19 | 3.12 ± 0.5 | 0.381 | − 0.24 ± 0.18 | 0.76 ± 0.2 | 1.87 ± 0.24 | 3.26 ± 0.52 | 1.11 ± 0.23 | 2.5 ± 0.51 | 1.38 ± 0.53 | 0.980 | 2.9E−03 | 2.5E−12 | 2.1E−08 | 3.0E−05 | 3.4E−05 | 0.180 |
Aβ40 (n = 102) | 0.17 ± 0.1 | − 0.58 ± 0.17 | 0.52 ± 0.14 | 1.55 ± 0.21 | 2.12 ± 0.54 | 0.831 | − 0.75 ± 0.19 | 1.11 ± 0.21 | 2.13 ± 0.27 | 2.71 ± 0.57 | 1.03 ± 0.25 | 1.6 ± 0.56 | 0.57 ± 0.58 | 2.5E−03 | 8.2E−06 | 2.1E−13 | 5.1E−05 | 8.7E−04 | 0.088 | 1.000 |
NfL (n = 101) | 0.15 ± 0.09 | 0.65 ± 0.14 | 0.84 ± 0.12 | 1.28 ± 0.17 | 2.01 ± 0.45 | 0.123 | 0.51 ± 0.16 | 0.18 ± 0.18 | 0.63 ± 0.22 | 1.35 ± 0.47 | 0.44 ± 0.21 | 1.17 ± 0.47 | 0.73 ± 0.48 | 4.4E−02 | 1.000 | 0.102 | 0.091 | 0.506 | 0.235 | 0.950 |
VAMP2 (n = 90) | 0.11 ± 0.1 | − 0.35 ± 0.16 | 0.69 ± 0.15 | 1.91 ± 0.21 | 3.27 ± 0.52 | 0.764 | − 0.46 ± 0.19 | 1.05 ± 0.22 | 2.26 ± 0.27 | 3.62 ± 0.55 | 1.22 ± 0.26 | 2.57 ± 0.54 | 1.36 ± 0.56 | 0.278 | 5.7E−05 | 9.3E−15 | 2.8E−09 | 5.3E−05 | 6.3E−05 | 0.287 |
NRGN (n = 102) | 0.09 ± 0.09 | 0.19 ± 0.14 | 1.45 ± 0.12 | 2.75 ± 0.18 | 4.74 ± 0.46 | 0.403 | 0.1 ± 0.16 | 1.26 ± 0.18 | 2.56 ± 0.22 | 4.55 ± 0.48 | 1.3 ± 0.21 | 3.29 ± 0.47 | 1.99 ± 0.49 | 1.000 | 3.0E−10 | 0.0E+00 | 0.0E+00 | 2.5E−08 | 2.6E−10 | 1.1E−03 |
AD dementia | ||||||||||||||||||||
BACE1 (n = 188) | 0.1 ± 0.09 | − 0.81 ± 0.13 | 0.41 ± 0.1 | 1.27 ± 0.11 | 2.27 ± 0.32 | 0.381 | − 0.91 ± 0.16 | 1.22 ± 0.16 | 2.08 ± 0.18 | 3.08 ± 0.35 | 0.86 ± 0.15 | 1.86 ± 0.34 | 1 ± 0.34 | 6.9E−07 | 1.1E−11 | 0.0E+00 | 0.0E+00 | 2.5E−07 | 1.4E−06 | 0.074 |
Aβ40 (n = 188) | 0.17 ± 0.1 | − 1.22 ± 0.15 | 0.06 ± 0.1 | 0.99 ± 0.12 | 1.33 ± 0.35 | 0.831 | − 1.38 ± 0.18 | 1.28 ± 0.18 | 2.21 ± 0.19 | 2.55 ± 0.38 | 0.93 ± 0.16 | 1.27 ± 0.37 | 0.34 ± 0.37 | 7.2E−13 | 6.6E−11 | 0.0E+00 | 1.7E−09 | 2.6E−07 | 1.3E−02 | 1.000 |
NfL (n = 188) | 0.15 ± 0.09 | 1.02 ± 0.12 | 1.5 ± 0.09 | 1.97 ± 0.1 | 2.54 ± 0.29 | 0.123 | 0.87 ± 0.15 | 0.48 ± 0.15 | 0.95 ± 0.16 | 1.52 ± 0.32 | 0.47 ± 0.13 | 1.04 ± 0.31 | 0.57 ± 0.31 | 1.4E−07 | 2.9E−02 | 1.2E−07 | 5.6E−05 | 1.1E−02 | 1.6E−02 | 0.762 |
VAMP2 (n = 167) | 0.11 ± 0.1 | − 0.95 ± 0.15 | 0.55 ± 0.11 | 1.5 ± 0.12 | 2.71 ± 0.37 | 0.764 | − 1.07 ± 0.18 | 1.5 ± 0.18 | 2.45 ± 0.2 | 3.67 ± 0.4 | 0.95 ± 0.16 | 2.17 ± 0.38 | 1.22 ± 0.39 | 2.0E−07 | 1.4E−13 | 0.0E+00 | 0.0E+00 | 2.8E−07 | 6.9E−07 | 3.7E−02 |
NRGN (n = 188) | 0.09 ± 0.09 | − 0.13 ± 0.12 | 1.32 ± 0.09 | 2.25 ± 0.1 | 3.57 ± 0.3 | 0.403 | − 0.22 ± 0.15 | 1.45 ± 0.15 | 2.38 ± 0.16 | 3.69 ± 0.32 | 0.93 ± 0.14 | 2.24 ± 0.31 | 1.32 ± 0.31 | 0.961 | 0.0E+00 | 0.0E+00 | 0.0E+00 | 5.4E−10 | 4.9E−11 | 7.1E−04 |