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Table 2 Differences between p-tau subgroups in demographic variables and protein levels in CSF. Raw levels of proteins were compared between p-tau subgroups

From: P-tau subgroups in AD relate to distinct amyloid production and synaptic integrity profiles

  Characteristics per p-tau subgroup p-values of p-tau subgroup comparisons
Controls (n = 98) Subgroup 1: p-tau ≤ 56 pg/ml (n = 94) Subgroup 2: p-tau 57–96 pg/ml (n = 147) Subgroup 3: p-tau 97–159 pg/ml (n = 89) Subgroup 4: p-tau > 159 pg/ml (n = 11) p-value of group difference Control-subgroup 1 Control-subgroup 2 Control-subgroup 3 Control-subgroup 4 Subgroup 1–2 Subgroup 1–3 Subgroup 1–4 Subgroup 2–3 Subgroup 2–4 Subgroup 3–4
Preclinical AD, n (percentagea) 0 (0%) 21 (22%) 20 (14%) 9 (10%) 1 (9.1%) 7.2E−05 n.t. n.t. n.t. n.t. 1.000 1.000 1.000 1.000 1.000 1.000
Prodromal AD, n (percentagea) 0 (0%) 32 (34%) 46 (31%) 21 (24%) 3 (27%) 2.4E−08 n.t. n.t. n.t. n.t. 1.4E−02 0.524 0.931 0.524 1.000 1.000
AD dementia, n (percentagea) 0 (0%) 41 (44%) 81 (55%) 59 (66%) 7 (64%) 1.1E−21 n.t. n.t. n.t. n.t. 0.0E+00 0.0E+00 8.9E−03 0.178 0.977 1.000
Age in years, mean ± sd 58.2 ± 7.9 63.6 ± 7.8 65.5 ± 6.9 66.6 ± 7.8 68.5 ± 8.6 6.0E−13 1.3E−05 2.0E−10 3.4E−10 7.4E−04 0.119 1.5E−02 0.080 0.179 0.208 0.581
Sex, female (%) 32 (33%) 33 (35%) 56 (38%) 52 (58%) 8 (73%) 4.2E−04 0.836 0.661 6.9E−03 0.056 0.822 1.2E−02 0.073 1.2E−02 0.088 0.696
APOE ε4 carriership (%) 28 (29%) 62 (66%) 93 (63%) 54 (61%) 7 (64%) 1.2E−07 0.0E+00 0.0E+00 1.0E−04 0.108 1.000 1.000 1.000 1.000 1.000 1.000
MMSE score, mean ± sd 28.5 ± 1.4 24.6 ± 4.7 23.9 ± 4.2 22.4 ± 4.8 22.5 ± 4.3 1.3E−28 1.8E−12 2.1E−22 3.7E−22 3.5E−06 0.072 6.1E−04 0.086 2.5E−02 0.282 0.987
Amyloid in pg/ml, mean ± sd 1139 ± 161 616 ± 119 607 ± 99 615 ± 95 596 ± 95 3.3E−48 2.7E−32 4.3E−39 1.4E−31 1.5E−07 0.846 0.953 0.846 0.846 0.846 0.846
t-tau in pg/ml, mean ± sd 207 ± 59 286 ± 106 568 ± 154 982 ± 252 1732 ± 359 2.4E−77 6.3E−10 1.4E−38 1.7E−31 7.2E−08 1.7E−31 5.7E−31 7.2E−08 6.0E−29 4.8E−08 7.6E−07
p-tau in pg/ml, mean ± sd 36.7 ± 9.3 42.9 ± 11 75.4 ± 11 116 ± 16 195 ± 23 4.0E−82 4.4E−06 4.2E−39 9.9E−32 7.8E−08 1.9E−38 3.2E−31 7.8E−08 2.2E−37 5.6E−08 7.8E−08
Abnormal t-tau status, n (%) 0 (0%) 15 (16%) 141 (96%) 89 (100%) 11 (100%) 2.2E−77 n.t. n.t. n.t. n.t. 0.0E+00 0.0E+00 0.0E+00 0.17 1 n.t.
Abnormal p-tau status, n (%) 0 (0%) 0 (0%) 147 (100%) 89 (100%) 11 (100%) 1.0E−93 n.t. n.t. n.t. n.t. n.t. n.t. n.t. n.t. n.t. n.t.
BACE1 in ng/ml, median (range) 1.68 (.77–3.37) 1.51 (.63–2.47) 1.93 (1.04–3.48) 2.51 (1.54–3.93) 3.60 (2.61–4.34) 2.1E−37 5.0E−03 2.0E−06 2.2E−18 1.3E−07 1.1E−13 2.2E−23 1.3E−07 7.0E−13 1.5E−07 7.4E−05
Aβ40 in ng/ml, median (range) 6.09 (3.44–10.68) 5.02 (2.0–8.92) 6.71 (3.32–12.20) 8.69 (3.59–13.95) 9.40 (7.81–15.79) 9.8E−34 2.8E−06 1.5E−02 8.4E−15 4.2E−06 3.3E−13 1.5E−23 2.2E−07 9.8E−13 1.1E−05 0.069
NfL in pg/ml, median (range) 245 (113–1594) 389 (147–1770) 467 (169–2322) 630 (304–1441) 809 (413–1743) 5.9E−37 5.5E−08 1.1E−20 3.4E−24 7.0E−07 4.5E−05 2.1E−14 3.1E−05 9.0E−09 4.1E−04 0.107
VAMP2 in pg/ml, median (range) 131 (40–275) 106 (28–229) 163 (82–288) 237 (84–398) 382 (269–522) 3.8E−41 2.9E−04 3.4E−07 6.9E−21 3.4E−07 8.3E−16 4.5E−24 3.4E−07 3.8E−15 3.2E−07 1.6E−05
NRGN in pg/ml, median (range) 262 (73–498) 250 (56–501) 431 (188–752) 657 (353–1268) 1060 (754–1915) 3.4E−63 0.735 9.3E−25 3.9E−30 8.1E−08 4.4E−25 9.2E−30 8.1E−08 4.3E−23 5.6E−08 1.2E−06
  1. Controls were cognitively normal and had normal CSF amyloid, t-tau, and p-tau. Abnormal t-tau and p-tau status were based on previously derived cutoffs of 349 and 56 pg/ml (further details are in the “Methods” section). Differences between p-tau subgroups in demographic variables were tested with ANOVA, Kruskal Wallis rank sum, or chi-square tests as appropriate, followed by pairwise t tests, Wilcoxon rank sum tests, or post hoc chi-square tests for subgroup comparisons as appropriate. Differences between p-tau subgroups in protein levels were all tested with the Kruskal Wallis rank sum test, followed by Wilcoxon rank sum tests. p-values were FDR-corrected for multiple tests between p-tau subgroups
  2. 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; n.t., not tested
  3. aRelative percentage in subgroup