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Table 4 Percent changes in cerebrospinal fluid amyloid precursor protein fragment levels and cerebrospinal fluid total tau/phosphorylated tau protein levels from baseline at day 28 across treatment groups

From: Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer’s disease: randomized, double-blind, placebo-controlled study

Safety analysis set Caucasian Japanese
Early AD Preclinical AD
Percent change from baseline at day 28 Placebo JNJ-54861911 Placebo JNJ-54861911
10 mg 50 mg 10 mg 50 mg
CSF sAPPα (μg/ml), n 12 15 15 6 6 6
 Mean (SD) − 2.60 (15.336) 88.74 (60.035) 114.28 (50.461) 11.96 (33.788) 61.37 (24.755) 82.49 (42.820)
 Median (range) − 6.14 (− 27.1; 23.2) 69.32 (28.4; 264.2) 121.38 (11.4; 187.7) 2.03 (− 21.1; 66.8) 60.22 (33.7; 104.2) 86.71 (11.6; 136.2)
 95% CI of mean (− 12.3; 7.1) (55.5; 122.0) (86.3; 142.2) (− 23.50; 47.42) (35.39; 87.35) (37.55; 127.42)
 LS mean 113.02 218.19 249.66 11.04 62.60 82.17
 Difference of LS means (SE) 1.93 (1.100) 2.21 (1.101) 51.57 (21.480) 71.13 (20.649)
 95% CI (1.59; 2.34) (1.82; 2.68) (5.49; 97.64) (26.84; 115.41)
CSF sAPPβ (μg/ml), n 12 15 15 6 6 6
 Mean (SD) − 2.05 (13.485) − 64.34 (10.208) − 90.70 (2.785) 12.40 (29.163) − 66.90 (5.222) − 91.30 (3.570)
 Median (range) − 5.32 (− 21.7; 22.7) − 67.25 (− 75.4; − 39.6) − 90.40 (− 96.7; − 85.3) 3.29 (− 17.5; 59.5) − 65.78 (− 76.1; −61.1) − 91.21 (− 96.5; − 86.0)
 95% CI of mean (− 10.6; 6.5) (− 70.0; − 58.7) (− 92.2; − 89.2) (− 18.20; 43.01) (− 72.38; − 61.42) (− 95.05; − 87.55)
 LS mean 142.68 51.70 13.51 11.98 − 65.86 − 91.91
 Difference of LS means (SE) 0.36 (1.113) 0.09 (1.116) − 77.84 (10.543) − 103.88 (10.196)
 95% CI (0.29; 0.45) (0.08; 0.12)   (− 100.45; − 55.23) (− 125.75; − 82.02)
CSF total sAPP (μg/ml), n 12 15 15 6 6 6
 Mean (SD) − 7.80 (13.442) − 13.34 (19.260) − 15.29 (20.330) 0.06 (16.444) − 1.55 (27.494) − 24.85 (21.689)
 Median (range) − 5.86 (− 34.4; 19.7) − 13.34 (− 41.3; 19.6) − 17.39 (− 44.7; 21.9) 1.73 (− 27.0; 22.8) − 10.40 (− 23.3; 51.2) − 16.94 (− 53.7; − 2.6)
 95% CI of mean (− 16.3; 0.7) (− 24.0; − 2.7) (− 26.6; − 4.0) (− 17.19; 17.32) (− 30.40; 27.31) (− 47.61; − 2.08)
 LS mean 734.76 701.82 679.71 0.49 − 2.16 − 24.65
 Difference of LS means (SE) 0.96 (1.087) 0.93 (1.086) − 2.65 (14.338) − 25.14 (13.383)
 95% CI (0.81; 1.13) (0.78; 1.09) (− 33.40; 28.10) (− 53.85; 3.56)
CSF total tau (ng/L), n 13 15 15 6 6 6
 Mean (SD) − 1.68 (4.130) 4.18 (7.629) 8.02 (6.557) − 17.00 (13.054) − 4.67 (48.718) − 38.83 (52.648)
 Median (range) − 2.48 (− 9.8; 5.6) 6.76 (− 11.2; 16.1) 7.64 (− 4.5; 23.4) − 20.50 (− 28.0; 7.0) − 21.00 (− 38.0; 90.0) − 32.50 (− 110.0; 250)
 95% CI of mean (− 4.18; 0.81) (− 0.04; 8.41) (4.39; 11.65) (− 30.70; − 3.30) (− 55.79; 46.46) (− 94.08; 16.42)
CSF P-tau (ng/L), n 12 15 14 6 6 6
 Mean (SD) − 1.55 (4.252) 3.56 (4.797) 7.36 (3.648) − 1.67 (2.422) − 0.67 (5.046) − 2.17 (6.911)
 Median (range) 0.00 (− 8.0; 5.4) 3.45 (− 4.6; 11.5) 7.42 (1.6; 16.7) − 1.00 (− 5.0; 1.0) − 2.00 (− 5.0; 9.0) − 0.50 (− 11.0; 5.0)
 95% CI of mean (− 4.26; 1.15) (0.91; 6.22) (5.25; 9.47) (− 4.21; 0.88) (− 5.96; 4.63) (− 9.42; 5.09)
  1. Abbreviations: AD Alzheimer’s disease, Amyloid-beta, CSF Cerebrospinal fluid, LS Least squares, sAPP Soluble amyloid precursor protein