Background
Methods
Centers and participants
Female
N = 211 | Male
N = 208 | Female | Male | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
IPD
N = 49 | PDLRRK2
N = 73 | CON
N = 89 | IPD
N = 95 | PDLRRK2
N = 69 | CON
N = 44 |
p value IPD PDLRRK2
CON |
p value Post hoc IPD CON |
p value Post hoc PDLRRK2
CON |
p value Post hoc IPD PDLRRK2
|
p value IPD PDLRRK2
CON |
p value Post hoc IPD CON |
p value Post hoc PDLRRK2
CON |
p value Post hoc IPD PDLRRK2
| |
Age Years | 68 46–83 | 67 35–89 | 57 18–83 | 69 46–80 | 65 36–88 | 58 28–83 | 0.001 | 0.001 | 0.001 | 0.999 | 0.001 | 0.001 | 0.012 | 0.204 |
Age at onset Years | 60 39–77 | 59 29–76 | 61 39–75 | 54 23–82 | 0.280 | 0.001 | ||||||||
Disease duration Years | 7 1–20 | 10 1–25 | 7 1–21 | 11 1–34 | 0.003 | 0.001 | ||||||||
UPDRS-III | 26 6–64 | 18 2–82 | 0 0–9 | 28 9–61 | 19 1–70 | 0 0–8 | 0.001 | 0.001 | 0.001 | 0.379 | 0.001 | 0.001 | 0.001 | 0.001 |
HY | 2 1–4 | 2 1–5 | 2 1–4 | 2 1–5 | 0.544 | 0.889 | ||||||||
MoCA | 27 11–30 | 25 6–30 | 27 17–30 | 27 13–30 | 24 5–30 | 27 17–30 | 0.001 | 0.999 | 0.001 | 0.014 | 0.001 | 0.999 | 0.002 | 0.001 |
RBD Questionnaire | 3 0–11 | 3 0–11 | 1 0–13 | 4 0–13 | 3 0–12 | 1 0–11 | 0.001 | 0.001 | 0.001 | 0.941 | 0.001 | 0.001 | 0.017 | 0.009 |
ESS | 9 1–18 | 6 0–24 | 6 0–15 | 10 0–23 | 8 0–24 | 6 0–14 | 0.002 | 0.002 | 0.999 | 0.024 | 0.001 | 0.001 | 0.246 | 0.057 |
SCOPA-AUT | 15 2–36 | 15 0–45 | 7 0–41 | 13 0–40 | 12 0–51 | 6 0–30 | 0.001 | 0.001 | 0.001 | 0.999 | 0.001 | 0.001 | 0.001 | 0.999 |
Regular anti-inflammatory medication (% of individuals) | 12.2 | 10.3 | 1.2 | 10.5 | 3.1 | 0.0 | 0.022 | 0.010 | 0.023 | 0.772 | 0.032 | 0.033 | 0.522 | 0.125 |
Female
N = 211 | Male
N = 208 | Female | Male | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Serum marker | IPD
N = 49 | PDLRRK2
N = 73 | CON
N = 89 | IPD
N = 95 | PDLRRK2
N = 69 | CON
N = 44 |
p value IPD PDLRRK2
CON |
p value Post hoc IPD CON |
p value Post hoc PDLRRK2
CON |
p value Post hoc IPD PDLRRK2
|
p value IPD PDLRRK2
CON |
p value Post hoc IPD CON |
p value Post hoc PDLRRK2
CON |
p value Post hoc IPD PDLRRK2
|
Alpha fetoprotein ng/ml | 0.97 0.09–6.20 | 0.81 0.12–4.07 | 0.76 0.07–6.94 | 1.17 0.14–7.17 | 0.93 0.12–14.10 | 0.95 0.33–3.52 | 0.004 | 0.008 | 0.017 | 0.014 | 0.034 | 0.070 | 0.849 | 0.032 |
BDNF (Brain-derived neurotrophic factor) ng/ml | 27.40 15.50–40.60 | 18.90 3.85–55.40 | 19.70 2.92–41.70 | 25.50 10.60–56.30 | 15.60 1.52–37.20 | 17.05 2.88–45.10 | <0.001 | <0.001 | 0.053 | <0.001 | <0.001 | <0.001 | 0.311 | <0.001 |
ENA-78 (Epithelial-derived neutrophil-activating peptide 78) ng/ml | 2.08 0.82–6.15 | 1.91 0.56–8.36 | 2.03 0.48–7.70 | 1.62 0.48–4.61 | 1.43 0.36–5.08 | 1.54 0.19–4.77 | 0.403 | 0.710 | 0.499 | 0.307 | 0.465 | 0.439 | 0.016 | 0.766 |
FABP (Fatty-acid-binding protein) ng/ml | 4.97 2.24–81.10 | 3.71 0.40–26.70 | 2.87 0.97–12.00 | 5.91 1.45–22.20 | 4.44 1.37–18.90 | 4.04 1.44–11.50 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.006 | 0.002 |
GH (Growth hormone) ng/ml | 1.39 0.11–14.40 | 2.47 0.08–26.50 | 1.61 0.11–29.60 | 0.79 0.04–14.90 | 0.87 0.08–30.80 | 0.36 0.07–24.50 | 0.145 | 0.326 | 0.415 | 0.117 | 0.004 | 0.083 | 0.005 | 0.030 |
ICAM-1 (Intercellular adhesion molecule 1) ng/ml | 152.62 65.70–224.00 | 161.00 73.50–262.00 | 160.00 80.00–288.00 | 149.00 71.60–273.00 | 150.00 51.60–246.00 | 150.50 83.40–232.00 | 0.340 | 0.544 | 0.722 | 0.018 | 0.251 | 0.183 | 0.529 | 0.267 |
IL-1-beta pg/ml | 2.18 1.02–4.97 | 1.83 0.29–4.53 | 1.84 0.56–4.10 | 2.57 1.11–17.10 | 2.38 0.71–5.22 | 2.17 1.02–3.30 | 0.052 | 0.018 | 0.726 | 0.239 | 0.012 | 0.019 | 0.179 | 0.033 |
IL-4 pg/ml | 16.80 8.20–33.20 | 15.10 5.57–27.00 | 15.10 6.73–31.50 | 15.90 5.16–41.20 | 13.20 4.43–27.10 | 13.10 5.02–27.00 | 0.097 | 0.409 | 0.083 | 0.095 | 0.024 | 0.070 | 0.671 | 0.030 |
IL-6 pg/ml | 4.36 1.67–20.30 | 4.26 1.27–16.30 | 3.65 1.27–99.10 | 5.29 1.67–13.90 | 5.63 2.00–13.70 | 4.71 2.17–9.57 | 0.008 | 0.017 | 0.053 | 0.020 | 0.033 | 0.346 | 0.002 | 0.254 |
IL-8 pg/ml | 9.72 2.85–38.10 | 12.90 3.17–60.70 | 11.60 3.60–60.30 | 10.70 2.94–771.00 | 12.30 2.93–209.00 | 10.75 2.65–77.50 | 0.052 | 0.025 | 0.242 | 0.232 | 0.332 | 0.428 | 0.145 | 0.054 |
IL-10 pg/ml | 4.68 1.72–36.10 | 3.72 1.78–19.20 | 3.26 1.78–21.80 | 5.09 2.55–36.90 | 3.29 1.78–13.80 | 3.26 1.78–7.59 | 0.001 | <0.001 | 0.392 | 0.032 | <0.001 | <0.001 | 0.488 | <0.001 |
IL-12-p40 ng/ml | 0.29 0.12–0.71 | 0.21 0.10–0.49 | 0.24 0.07–0.69 | 0.25 0.07–0.88 | 0.22 0.07–0.62 | 0.16 0.07–0.36 | 0.007 | 0.004 | 0.228 | 0.016 | <0.001 | <0.001 | 0.015 | 0.059 |
IL-16 pg/ml | 532.00 152.00–1000.00 | 543.00 237.00–1080.00 | 551.00 239.00–1370.00 | 522.00 224.00–1580.00 | 497.00 232.00–1310.00 | 520.00 268.00–760.00 | 0.537 | 0.265 | 0.535 | 0.663 | 0.611 | 0.851 | 0.603 | 0.403 |
IL-18 pg/ml | 282.00 147.00–546.00 | 272.00 101.00–752.00 | 282.00 140.00–3360.00 | 304.00 137.00–925.00 | 312.00 133.00–771.00 | 306.00 141.00–681.00 | 0.521 | 0.390 | 0.725 | 0.362 | 0.094 | 0.812 | 0.040 | 0.020 |
Leptin ng/ml | 17.50 4.83–56.20 | 17.80 0.66–113.00 | 15.70 2.10–123.00 | 6.59 0.69–46.00 | 6.74 0.63–32.40 | 7.06 1.14–32.50 | 0.934 | 0.460 | 0.624 | 0.951 | 0.534 | 0.781 | 0.162 | 0.631 |
MCP-1 (Monocyte chemotactic protein 1) pg/ml | 396.00 177.00–941.00 | 366.00 152.00–1190.00 | 342.00 113.00–844.00 | 448.00 21.90–872.00 | 333.00 99.90–802.00 | 323.50 120.00–916.00 | 0.511 | 0.268 | 0.922 | 0.136 | 0.066 | 0.006 | 0.389 | 0.115 |
MDC (Macrophage-derived chemokine) pg/ml | 425.00 292.00–676.00 | 516.00 125.00–964.00 | 474.00 93.80–1800.00 | 401.00 171.00–838.00 | 407.00 146.00–3860.00 | 483.00 188.00–950.00 | 0.113 | 0.289 | 0.286 | 0.014 | 0.014 | 0.017 | 0.381 | 0.036 |
MIP-1-beta (Macrophage inflammatory protein-1-beta) pg/ml | 251.00 70.50–1160.00 | 217.00 18.40–588.00 | 215.00 62.20–955.00 | 237.00 29.70–737.00 | 207.00 75.90–1530.00 | 208.00 69.40–2520.00 | 0.034 | 0.011 | 0.097 | 0.264 | 0.762 | 0.536 | 0.491 | 0.189 |
MMP-3 (Matrix-metallo-proteinase-3) ng/ml | 14.80 4.42–37.10 | 13.50 6.31–120.00 | 12.30 6.08–92.90 | 23.00 7.28–59.90 | 24.00 8.01–48.40 | 23.55 9.61–53.80 | 0.013 | 0.052 | 0.029 | 0.057 | 0.594 | 0.891 | 0.703 | 0.283 |
MMP-9 (Matrix-metallo-proteinase-9) ng/ml | 16.80 6.80–28.00 | 20.90 9.28–46.20 | 19.60 12.60–61.60 | 21.20 12.10–42.30 | 27.00 15.60–121.00 | 25.40 16.10–37.80 | <0.000 | <0.001 | 0.100 | <0.001 | <0.001 | 0.222 | 0.058 | <0.001 |
SCF (Stem cell factor) pg/ml | 319.00 169.00–535.00 | 269.00 78.30–635.00 | 277.00 117.00–614.00 | 293.00 154.00–514.00 | 251.00 81.90–587.00 | 279.00 127.00–494.00 | <0.001 | <0.001 | 0.016 | 0.009 | 0.001 | 0.004 | 0.344 | <0.001 |
TF (Tissue factor) ng/ml | 0.28 0.08–0.72 | 0.25 0.12–0.67 | 0.24 0.07–0.53 | 0.43 0.08–23.80 | 0.32 0.13–0.74 | 0.30 0.15–0.43 | 0.064 | 0.231 | 0.002 | 0.833 | 0.011 | 0.057 | 0.187 | 0.102 |
TNF-alpha (Tumor necrosis factor alpha) pg/ml | 58.70 11.70–110.00 | 60.00 21.20–129.00 | 60.00 27.60–110.00 | 76.50 39.20–187.00 | 73.30 30.30–143.00 | 69.30 49.80–105.00 | 0.666 | 0.294 | 0.925 | 0.427 | 0.200 | 0.299 | 0.161 | 0.296 |
TPO (Thrombopoietin) pg/ml | 2.67 1.75–3.55 | 2.07 0.19–3.76 | 2.37 0.56–4.48 | 2.54 1.62–3.68 | 1.98 0.31–4.08 | 2.25 0.59–3.64 | <0.001 | 0.002 | 0.042 | 0.001 | <0.001 | <0.001 | 0.069 | <0.001 |
Female
N = 152 | Male
N = 96 | Female | Male | |||
---|---|---|---|---|---|---|
NMCLRRK2
N = 63 | CON
N = 89 | NMCLRRK2
N = 52 | CON
N = 44 |
p value NMCLRRK2
CON |
p value NMCLRRK2
CON | |
Age Years | 51 23–84 | 57 18–83 | 54 27–82 | 58 28–83 | 0.087 | 0.110 |
UPDRS-III | 0 0–13 | 0 0–9 | 0 0–15 | 0 0–8 | 0.021 | 0.542 |
MoCA | 28 18–30 | 27 17–30 | 27 18–30 | 27 17–30 | 0.756 | 0.809 |
RBD Questionnaire | 1 0–9 | 1 0–13 | 2 0–9 | 1 0–11 | 0.396 | 0.943 |
ESS | 6 0–15 | 6 0–15 | 5 0–15 | 6 0–14 | 0.948 | 0.399 |
SCOPA-AUT | 8 1–33 | 7 0–41 | 7 0–39 | 6 0–30 | 0.221 | 0.729 |
Regular anti-inflammatory medication (% of individuals) | 3.7 | 1.2 | 4.6 | 0.0 | 0.561 | 0.495 |
Female
N = 152 | Male
N = 96 | Female | Male | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Serum Marker | NMCLRRK2
N = 63 | NMCLRRK2
Prodromal
N = 18 | CON
N = 89 | NMCLRRK2
N = 52 | NMCLRRK2
Prodromal
N = 15 | CON
N = 44 |
p value NMCLRRK2
CON |
p value NMCLRRK2
Prodromal CON |
p value NMCLRRK2
CON |
p value NMCLRRK2
Prodromal CON |
Alpha fetoprotein ng/ml | 0.59 0.06–3.53 | 0.58 0.19–2.28 | 0.76 0.07–6.94 | 0.89 0.14–2.47 | 0.93 0.31–2.47 | 0.95 0.33–3.52 | 0.004 | 0.051 | 0.068 | 0.281 |
BDNF (Brain-derived neurotrophic factor) ng/ml | 17.50 3.30–41.70 | 26.20 3.85–41.70 | 19.70 2.92–41.70 | 13.00 1.40–40.50 | 6.98 1.74–36.60 | 17.05 2.88–45.10 | 0.376 | 0.258 | 0.026 | 0.128 |
ENA-78 (Epithelial-derived neutrophil-activating peptide 78) ng/ml | 2.14 0.38–5.77 | 2.26 0.38–5.76 | 2.03 0.48–7.70 | 1.63 0.46–5.98 | 1.71 0.46–3.75 | 1.54 0.19–4.77 | 0.610 | 0.811 | 0.016 | 0.203 |
FABP (Fatty-acid-binding protein) ng/ml | 2.87 0.88–14.40 | 3.03 1.62–7.99 | 2.87 0.97–12.00 | 3.71 2.05–17.80 | 3.80 2.44–17.80 | 4.04 1.44–11.50 | <0.001 | <0.001 | <0.001 | 0.096 |
GH (Growth hormone) ng/ml | 2.18 0.08–35.60 | 3.16 0.08–30.30 | 1.61 0.11–29.60 | 0.35 0.06–6.28 | 0.36 0.06–1.37 | 0.34 0.07–24.50 | 0.109 | 0.266 | 0.175 | 0.270 |
ICAM-1 (Intercellular adhesion molecule 1) ng/ml | 156.00 103.00–317.00 | 157.50 121.00–224.00 | 160.00 80.00–288.00 | 154.50 99.10–329.00 | 155.00 99.10–329.00 | 150.50 83.40–232.00 | 0.839 | 0.930 | 0.085 | 0.632 |
IL-1-beta pg/ml | 1.76 0.71–4.41 | 2.07 0.94–4.41 | 1.84 0.56–4.10 | 2.22 0.78–4.68 | 2.46 0.78–3.67 | 2.17 1.02–3.30 | 0.427 | 0.072 | 0.471 | 0.158 |
IL-4 pg/ml | 15.90 4.89–30.00 | 15.80 9.01–26.80 | 15.10 6.73–31.50 | 13.10 5.02–23.60 | 14.82 8.19–20.90 | 14.00 5.02–27.00 | 0.562 | 0.458 | 0.333 | 0.692 |
IL-6 pg/ml | 3.65 1.05–10.60 | 3.71 2.11–8.77 | 3.65 1.27–99.10 | 4.42 2.50–17.50 | 4.87 2.50–10.30 | 4.71 2.17–9.57 | 0.062 | 0.039 | 0.246 | 0.223 |
IL-8 pg/ml | 10.70 4.89–30.00 | 10.85 3.17–84.00 | 11.60 3.60–60.30 | 10.30 2.36–39.20 | 10.50 6.53–39.20 | 10.75 2.65–77.50 | <0.001 | 0.039 | 0.029 | 0.288 |
IL-10 pg/ml | 3.57 1.78–32.80 | 3.61 1.80–9.69 | 3.26 1.78–7.70 | 3.44 1.78–9.96 | 3.49 1.78–9.96 | 3.26 1.78–7.59 | 0.910 | 0.809 | 0.820 | 0.932 |
IL-12-p40 ng/ml | 0.24 0.07–0.77 | 0.24 0.07–0.77 | 0.24 0.07–0.69 | 0.19 0.08–0.38 | 0.22 0.09–0.38 | 0.16 0.07–0.36 | 0.010 | 0.001 | 0.294 | 0.432 |
IL-16 pg/ml | 497.00 177.00–752.00 | 532.50 342.00–735.00 | 551.00 239.00–1370.00 | 524.00 261.00–1060.00 | 549.00 419.00–815.00 | 520.00 268.00–760.00 | 0.007 | 0.197 | 0.100 | 0.281 |
IL-18 pg/ml | 288.00 110.00–15000.00 | 290.00 152.00–440.00 | 282.00 140.00–3360.00 | 313.00 165.00–872.00 | 333.00 186.00–872.00 | 306.00 141.00–681.00 | 0.551 | 0.828 | 0.083 | 0.084 |
Leptin ng/ml | 17.10 1.90–90.60 | 24.25 7.16–44.70 | 15.70 2.10–123.00 | 7.03 1.48–38.40 | 9.90 3.60–31.90 | 7.06 1.14–32.50 | 0.674 | 0.035 | 0.314 | 0.475 |
MCP-1 (Monocyte chemotactic protein 1) pg/ml | 333.00 40.80–854.00 | 325.50 199.00–635.00 | 342.00 113.00–844.00 | 329.50 12.20–740.00 | 292.00 12.20–667.00 | 323.50 120.00–916.00 | 0.246 | 0.631 | 0.148 | 0.290 |
MDC (Macrophage-derived chemokine) pg/ml | 452.00 216.00–981.00 | 539.50 216.00–981.00 | 474.00 93.80–1800.00 | 464.00 217.00–855.00 | 423.00 261.00–774.00 | 483.00 188.00–950.00 | 0.514 | 0.504 | 0.249 | 0.692 |
MIP-1-beta (Macrophage inflammatory protein-1-beta) pg/ml | 183.00 61.50–720.00 | 240.00 61.50–436.00 | 215.00 62.20–955.00 | 167.00 77.20–736.00 | 220.00 77.20–736.00 | 208.00 69.40–2520.00 | 0.607 | 0.302 | 0.240 | 0.604 |
MMP-3 (Matrix-metallo-proteinase-3) ng/ml | 10.70 4.04–66.60 | 12.70 6.32–66.60 | 12.30 6.08–92.90 | 21.35 11.30–46.80 | 21.00 11.90–45.20 | 23.55 9.61–53.80 | <0.001 | 0.055 | 0.418 | 0.600 |
MMP-9 (Matrix-metallo-proteinase-9) ng/ml | 20.40 10.80–40.90 | 22.45 11.90–40.90 | 19.60 12.60–61.60 | 25.70 16.10–36.10 | 25.30 16.10–36.10 | 25.40 16.10–37.80 | 0.009 | 0.007 | 0.762 | 0.931 |
SCF (Stem cell factor) pg/ml | 264.00 154.00–520.00 | 263.00 193.00–404.00 | 277.00 117.00–614.00 | 280.00 145.00–635.00 | 299.00 190.00–458.00 | 279.00 127.00–494.00 | 0.013 | 0.037 | 0.076 | 0.166 |
TF (Tissue factor) ng/ml | 0.24 0.12–0.57 | 0.26 0.15–0.57 | 0.24 0.07–0.53 | 0.29 0.13–1.67 | 0.32 0.16–0.48 | 0.30 0.15–0.43 | 0.004 | 0.004 | 0.514 | 0.464 |
TNF-alpha (Tumor necrosis factor alpha) pg/ml | 54.30 27.60–106.00 | 55.75 41.60–106.00 | 60.00 27.60–110.00 | 74.60 33.00–103.00 | 78.30 38.40–98.60 | 69.30 49.80–105.00 | 0.752 | 0.652 | 0.149 | 0.262 |
TPO (Thrombopoetin) pg/ml | 2.08 0.19–3.86 | 2.24 0.22–3.49 | 2.37 0.56–4.48 | 1.62 0.55–4.18 | 2.05 0.55–3.87 | 2.37 0.59–3.64 | 0.175 | 0.204 | 0.082 | 0.115 |