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Table 4 Differences in protein levels between p-tau subgroups depending on cognitive stage

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
  1. Protein levels were natural log-transformed and standardized relative to cognitively normal individuals with normal CSF amyloid, t-tau, and p-tau (controls). Estimates of protein level differences between p-tau subgroups are corrected for age and sex and were calculated with linear models which included an interaction term with clinical diagnostic group. p-values of comparisons between p-tau subgroups, and between p-tau subgroup 1 and controls, were adjusted with the Sidak method (considered significant at p-value < 0.05)
  2. CSF, cerebrospinal fluid; BACE1, beta-site amyloid precursor protein cleaving enzyme 1; Aβ40, amyloid-beta 1–40; NfL, neurofilament light; NRGN, neurogranin; VAMP2, vesicle-associated membrane protein 2