Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease

Jing Zhang, Hayley A. Mattison, Changqin Liu, Carmen Ginghina, Peggy Auinger, Michael P. McDermott, Tessandra Stewart, Un Jung Kang, the Parkinson Study Group DATATOP Investigators, Kevin C. Cain, Min Shi

I. Supplementary Figures

a. b. c.

d. e. f.

Suppl. Fig. 1 Age dependence of Aβ42, t-tau, and p-tau in CSF.

CSF amyloid beta peptide 1-42 (Aβ42) (a), total tau (t-tau) (b), and phosphorylated tau (p-tau) (c) concentrations were measured in individual samples collected at baseline using Luminex assays. Except for Aβ42 and p-tau/t-tau, all other CSF markers were log transformed due to non-normal distribution. Concentrations of t-tau (b) and p-tau (b), along with t-tau/Aβ42 (e) and p-tau/Aβ42 (f) in CSF, all tended to increase with age (t-tau: r=0.373, p<0.00001; p-tau: r=0.269, p<0.00001; t-tau/Aβ42: r=0.364, p<0.00001; p-tau/Aβ42: r=0.217, p=0.000011), while the p-tau/t-tau ratio (d) tended to decrease with age (r=-0.112, p=0.025). Concentrations of Aβ42 (a) were largely stable with respect to age (r=0.087, p=0.08).

a. b.

c. d.

e. f.

Suppl. Fig. 2 Comparison of rate of CSF marker changes among treatment groups. CSF amyloid beta peptide 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) concentrations were measured in individual samples collected at baseline and final (endpoint or the end of Period II) time points using Luminex assays. The subjects were treated with placebo (No drug), deprenyl (selegiline; DEP), α-tocopherol (vitamin E; TOC), or both (TOC/DEP) during Period I, though those who did not reach endpoint during Period I were all treated with DEP in Period II. Shown are the rates of change (average change per month) between the two time points for Aβ42 (a), t-tau (b), p-tau (c), p-tau/t-tau (d), t-tau/Aβ42 (e), and p-tau/Aβ42 (f) in four treatment groups. For each treatment group, the bottom and top of the box represent the 25th and 75th percentile (the lower and upper quartiles, respectively), the band near the middle of the box represents the 50th percentile (the median), and the ends of the whiskers represent the lowest datum still within 1.5 interquartile range (IQR) of the lower quartile, and the highest datum still within 1.5 IQR of the upper quartile, respectively.


II. Supplementary Tables

Suppl. Table 1 APOE genotypes* and baseline clinical and CSF marker values

Without ε4 allele / With ε4 allele
ε3, ε3 / ε2, ε3 / total / ε4, ε4 / ε3, ε4 / ε2, ε4 / total
Number of cases / 181 / 35 / 216 / 2 / 58 / 3 / 63
Age (year)†,
range / 59.9±9.3
34-79 / 59.1±8.0
41-77 / 59.7±9.1
34-79 / 56.0±1.4
55-57 / 59.9±7.4
37-73 / 58.7±16.2
40-69 / 59.7±7.7
37-73
MMSE†,
range / 29.0±1.4
23-30 / 29.2±1.1
27-30 / 29.0±1.3
23-30 / 28.5±2.1
27-30 / 28.7±1.4
25-30 / 28.0±2.6
25-30 / 28.7±1.5
25-30
UPDRS total†,
range / 23.4±11.1
1.0-59.5 / 23.1±11.6
6.5-53.0 / 23.3±11.2
1.0-59.5 / 22.5±5.7
18.5-26.5 / 23.7±10.3
8.0-51.5 / 43.8±22.0
19.0-61.0 / 24.6±11.5
8.0-61.0
UPDRS motor†,
range / 15.6±8.3
1.0-41.5 / 15.0±8.1
4.5-35.0 / 15.5±8.3
1.0-41.5 / 13.5±7.1
8.5-18.5 / 16.4±8.0
4.0-38.5 / 31.5±13.5
16.0-41.0 / 17.0±8.8
4.0-41.0
CSF Aβ42 (pg/ml) †,
range / 247.5±76.3
74.8-670.1 / 247.9±67.0
119.3-367.1 / 247.6±74.8
74.8-670.1 / 214.6±22.8
198.5-230.7 / 207.1±69.5
52.1-368.5 / 193.5±51.3
137.2-237.7 / 206.7±67.4
52.1-368.5
CSF t-tau (pg/ml) †,
range / 44.9±23.8
14.0-213.6 / 46.7±20.9
19.4-104.8 / 45.2±23.4
14.0-213.6 / 34.5±8.2
28.7-40.3 / 42.2±22.2
16.4-140.6 / 69.9±46.7
30.8-121.7 / 43.3±23.7
16.4-140.6
CSF p-tau (pg/ml) †,
range / 23.0±10.5
4.0-74.0 / 23.6±10.5
6.5-47.7 / 23.1±10.5
4.0-74.0 / 15.4±14.0
5.5-25.4 / 21.6±9.1
4.9-40.4 / 31.2±18.9
17.7-52.8 / 21.9±9.8
4.9-52.8
CSF p-tau/t-tau†,
range / 0.551±0.205
0.136-1.061 / 0.546±0.246
0.172-1.064 / 0.550±0.212
0.136-1.064 / 0.411±0.309
0.193-0.629 / 0.563±0.223
0.155-1.021 / 0.499±0.229
0.309-0.753 / 0.555±0.223
0.155-1.021
CSF t-tau/Aβ42†,
range / 0.185±0.101
0.076-1.215 / 0.190±0.073
0.112-0.439 / 0.185±0.097
0.076-1.215 / 0.160±0.021
0.145-0.175 / 0.216±0.119
0.086-0.726 / 0.425±0.401
0.150-0.886 / 0.224±0.143
0.086-0.886
CSF p-tau/Aβ42†,
range / 0.097±0.050
0.024-0.421 / 0.097±0.040
0.031-0.200 / 0.097±0.049
0.024-0.421 / 0.069±0.058
0.028-0.110 / 0.113±0.056
0.028-0.293 / 0.190±0.169
0.074-0.384 / 0.116±0.065
0.028-0.384

* Among the 403 subjects included in this study, APOE genotypes are known for 279 subjects. † Mean ± SD.

Suppl. Table 2 Predicting and progression tracking values of selected CSF markers

Covariates / Default* / Default + baseline UPDRS / Default + baseline UPDRS + baseline MMSE
Prediction (correlation between baseline CSF marker and rate of UPDRS change)
CSF p-tau/t-tau vs UPDRS total / r=-0.136, p=0.007 / r=-0.137, p=0.006 / r=-0.145, p=0.004
CSF p-tau/t-tau vs UPDRS motor / r=-0.118, p=0.019 / r=-0.117, p=0.02 / r=-0.125, p=0.013
CSF p-tau/Aβ42 vs UPDRS total / r=-0.171, p=0.001 / r=-0.166, p=0.001 / r=-0.163, p=0.001
CSF p-tau/Aβ42 vs UPDRS motor / r=-0.146, p=0.004 / r=-0.141, p=0.005 / r=-0.137, p=0.006
Progression (correlation between rate of CSF marker change and rate of UPDRS change)
CSF t-tau vs UPDRS total / r=0.165, p=0.001 / r=0.174, p=0.0005 / r=0.156, p=0.002
CSF t-tau vs UPDRS motor / r=0.147, p=0.003 / r=0.155, p=0.002 / r=0.134, p=0.008
CSF t-tau/Aβ42 vs UPDRS total / r=0.13, p=0.01 / r=0.135, p=0.007 / r=0.123, p=0.014
CSF t-tau/Aβ42 vs UPDRS motor / r=0.13, p=0.01 / r=0.137, p=0.006 / r=0.124, p=0.014

* Age and sex of subjects, treatment group, and length of time exposed to deprenyl (DEP).

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