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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