Table 4.
Salivary biomarkers for PD.
| Study (Author/Year) |
Biomarker Tested | Biomarker/ Concentration (Saliva) |
Detection Method (Saliva) |
Body Fluids Tested |
|---|---|---|---|---|
| 1. Devic et al., 2011 [28] |
Total α-Syn | Total α-Syn markedly (but non-significantly) reduced in PD compared to controls: PD: 70 ± 80 pg/mL Control: 110 ± 130 pg/mL α-Syn depletion markedly correlated (but non-significantly) with UPDRS scores (i.e., disease severity) |
Luminex IP/Western blot |
Saliva |
| DJ-1 | DJ-1 moderately (but non-significantly) increased in PD compared to controls: PD: 190 ± 70 ng/mL Control: 120 ± 30 ng/mL DJ-1 enrichment did not correlate with UPDRS scores (i.e., disease severity) |
Luminex IP/Western blot |
Saliva | |
| 2a. Kang et al., 2014 (pilot study) [29] |
DJ-1 | Moderate correlation between salivary DJ-1 levels and striatal dopaminergic function |
Luminex | Saliva |
| 2b. Kang et al., 2014 (large cohort study) [29] |
DJ-1 | DJ-1 levels were unaltered in PD patients compared to controls: PD: 4.11 ± 5.88 ng/mL Control: 3.86 ± 5.44 ng/mL DJ-1 enrichment did not correlate with UPDRS III scores (i.e., disease severity) |
Luminex | Saliva |
| 3. Stewart et al., 2014 [30] |
Total α-Syn | Total α-Syn slightly (but non-significantly) increased in cellular components of saliva in PD patients compared to controls (data extracted from paper graph): PD: 0.42 ± 0.09 pg/μg Control: 0.36 ± 0.03 pg/μg |
Luminex | Cellular components of saliva |
| DJ-1 | DJ-1 levels were unaltered in cellular components of saliva in PD patients vs. controls (data extracted from paper graph): PD: 88 ± 8 pg/μg Control: 70 ± 8 pg/μg |
Luminex | Cellular components of saliva | |
| 4. Al-Nimer et al., 2014 [31] | Total α-Syn | Total α-Syn significantly reduced in PD compared to controls: PD 65 ± 52.2 pg/mL Control: 314.01 ± 435.9 pg/mL |
ELISA | Saliva |
| 5. Masters et al., 2015 [32] | DJ-1 | DJ-1 levels significantly elevated in PD patients compared to controls: PD: 0.84 µg/mL Control: 0.42 µg/mL After normalization for total protein concentration, no alteration of DJ-1 in PD patients compared to controls Normalized DJ-1 levels correlated with UPDRS scores (i.e., disease severity) |
Western blot | Saliva |
| 6. Kang et al., 2016 [33] | Total α-Syn | Total α-Syn levels unaltered in PD patients compared to controls: PD: 128.66 ± 98.21 pg/mg Control: 131.31 ± 104.2 pg/mg |
Luminex | Saliva |
| Oligomeric α-Syn/ total α-Syn ratio |
Oligomeric α-Syn/total α-Syn significantly decreased in early disease state (HY I), but significantly increased in later disease states (HY II to IV) |
Western blot after size exclusion chromatography | Saliva | |
| 7. Vivacqua et al., 2016 [34] | Total α-Syn | Total α-Syn significantly reduced in PD patients compared to controls: PD: 5.08 ± 3.01 pg/mL Control: 31.3 ± 22.4 pg/mL |
ELISA | Saliva |
| Oligomeric α-Syn | Oligomeric α-Syn significantly increased in PD patients compared to controls: PD: 1.062 ± 0.266 ng/mL Control: 0.498 ± 0.203 ng/mL |
ELISA | Saliva | |
| Oligomeric α-Syn/ total α-Syn ratio |
Oligomeric α-Syn/total α-Syn ratio significantly increased in PD patients compared to controls: PD: 0.174 ± 0.044 Control: 0.065 ± 0.027 |
ELISA | Saliva | |
| 8. Goldman et al., 2018 [35] | Total α-Syn | Total α-Syn moderately (but non-significantly) increased in PD patients compared to controls: PD: 285.42 ± 400.13 pg/mL Control: 165.97 ± 272.3 pg/mL |
ELISA | Saliva CSF Plasma |
| 9. Su et al., 2018 [36] |
Total α-Syn | Total α-Syn significantly reduced in PD patients compared to controls: PD: 1269.02 ± 16.09 pg/mL Control: 1350.51 ± 25.79 pg/mL |
ELISA | Saliva |
| DJ-1 | DJ-1 levels significantly decreased in PD patients compared to controls: PD: 6.07 ± 3.23 ng/mL Control: 8.43 ± 4.33 ng/mL |
ELISA | Saliva | |
| 10.a Cao et al., 2019 [37] | Total α-Syn | Total α-Syn in PD patients unaltered compared to controls: PD: 11.93 (6.23~28.11) pg/ng Control: 12.23 (5.47~58.83) pg/ng (mean and interquartile range) |
Extracellular Vesicle Enrichment Kit followed by ECL immunoassays | Extracellular vesicles in saliva |
| Oligomeric α-Syn | Oligomeric α-Syn in PD patients significantly increased compared to controls: PD: 7.03 (3.58~12.11) pg/ng Control: 0.92 (0.49~1.61) pg/ng (mean and interquartile range) |
Extracellular Vesicle Enrichment Kit followed by ECL immunoassays | Extracellular vesicles in saliva | |
| Oligomeric α-Syn/ total α-Syn ratio |
Oligomeric α-Syn/total α-Syn ratio significantly increased in PD patients compared to controls: PD: 0.79 (0.23~1.82) Control: 0.10 (0.04~0.28) (mean and interquartile range) |
Extracellular Vesicle Enrichment Kit followed by ECL immunoassays | Extracellular vesicles in saliva | |
| 10b. Cao et al., 2020 [38] | Total α-Syn | Total α-Syn increased in PD patients compared to MSA-P patients: PD: 8.07 ± 4.71 pg/ng MSA-P: 5.44 ± 1.50 pg/ng |
Extracellular Vesicle Enrichment Kit followed by ECL immunoassays | Extracellular vesicles in saliva |
| Oligomeric α-Syn | Oligomeric α-Syn unaltered in PD patients compared to MSA-P patients: PD: 8.25 ± 3.98 pg/ng MSA-P: 7.29 ± 4.44 pg/ng |
Extracellular Vesicle Enrichment Kit followed by ECL immunoassays | Extracellular vesicles in saliva | |
| 11. Vivacqua et al., 2019 [39] | Total α-Syn | Total α-Syn significantly reduced in PD patients compared to control and to PSP: PD: 7.104 ± 5.122 pg/mL PSP: 29.091 ± 18.677 pg/mL Control: 28.444 ± 25.877 pg/mL |
ELISA | Saliva |
| Oligomeric α-Syn | Oligomeric α-Syn significantly increased in PD patients compared to controls: PD: 0.893 ± 1.949 ng/mL Control: 0.217 ± 0.191 ng/mL |
ELISA | Saliva | |
| Oligomeric α-Syn/ total α-Syn ratio |
Oligomeric α-Syn/total α-Syn ratio significantly increased in PD patients compared to controls: PD: 0.235 ± 0.793 Control: 0.0126 ± 0.0079 |
ELISA | Saliva | |
| 12. Shaheen et al., 2020 [40] |
Total α-Syn | Total α-Syn levels significantly reduced in PD patients compared to controls: PD: 159.4 ± 61.6 ng/mL Control: 229.9 ± 64 ng/mL |
ELISA | Saliva |
| Oligomeric α-Syn | Oligomeric α-Syn levels significantly increased in PD patients compared to controls: PD: 47.8 ± 11.8 ng/mL Control: 39.2 ± 9.2 ng/mL |
ELISA | Saliva | |
| Oligomeric α-Syn/ total α-Syn ratio |
Oligomeric α-Syn/total α-Syn ratio significantly increased in PD patients compared to controls: PD: 0.35 ± 0.18 Control: 0.19 ± 0.08 |
ELISA | Saliva | |
| 13. Chahine et al., 2020 [41] |
Total α-Syn | Total α-Syn non-significantly altered in saliva of PD patients compared to controls: PD: 65.6 ± 42.1 pg/mL Early PD: 49.2 ± 25.4 pg/mL Moderate PD: 63.1 ± 30.3 pg/mL Advanced PD: 83.7 ± 57.9 pg/mL Control: 64.4 ± 60.7 pg/mL |
ELISA | Blood CSF Saliva |
| 14. Fernández-Espejo et al., 2021 [42] |
Total α-Syn | Total α-Syn levels non-significantly decreased in PD patients compared to controls: PD: 361.89 ± 89 pg/mL Control: 372.1 ± 92 pg/mL |
ELISA | Serum Saliva human submandibular gland tissue |
ECL: electrochemiluminescence; IP: immunoprecipitation; NS: not specified. Biomarker concentrations of main population groups are underlined.