Table 2.
Potential biomarkers for early diagnosis of PD.
| Biomarkers | Strength levela | Sensitivityb | Specificityb | Approximate relative risk | Testing costc | References |
|---|---|---|---|---|---|---|
| Symptomatic biomarkers | ||||||
| Motor testing | Moderate | High (UPDRS > 4 identified prodromal parkinsonism with 88% sensitivity) | High (UPDRS > 4 identified prodromal parkinsonism with 94% specificity) | 3–4 | Moderate | [18, 19] |
| RBD | High | Low (~50% of PD patients occur RBD in 2 years) | High (76% risk of PD at 10 years) | 50 | High | [17, 21, 22] |
| Olfactory dysfunction | High | High (>80% of early PD) | Low | 5 | Low | [25–27] |
| Constipation | High | Moderate | Low (15%–20% prevalence in general population) | 2–2.5 | Low | [19, 29] |
| Depression | Moderate | Low (30%–40% of PD) | Low | 1.8 | Low | [19, 31] |
| Other autonomic symptoms | Low | Low | Low | 1.5–2.5 | Low | [19] |
| Imaging biomarkers | ||||||
| Dopaminergic PET/SPECT | Moderate | High (98% to detect nigrostriatal cell loss) | High | 20 | High | [32–34] |
| MRI | Low | Not estimated | Not estimated | Not estimated | High | [39, 40] |
| TCS | Moderate | Inconsistent | Inconsistent | 15 | Moderate | [44, 45] |
| MIBG scintigraphy | Moderate | High (88%) | High (85%) | Not estimated | High | [35–38] |
| Biochemical biomarkers | ||||||
| Plasma urate | Low | Not estimated | Not estimated | Hazard ratio 0.7–0.8 | Moderate | [50, 51] |
| Plasma apolipoprotein A1 | Low | Not estimated | Not estimated | Hazard ratio 0.742 | Moderate | [52, 53] |
| Plasma NAMPT | Low | High | High | Not estimated | Moderate | [54] |
| α-synuclein gastrointestinal biopsy | Low | Inconsistent | Inconsistent | Not estimated | High | [56–59] |
| α-synuclein skin biopsy | Low | High (80% sensitivity in early PD) | High (nearly 100%) | Not estimated | High | [60, 61] |
| α-synuclein submandibular biopsy | Low | High | High | Not estimated | High | [62, 63] |
MIBG, I-123-metaiodobenzylguanidine; MRI, magnetic resonance imaging; NAMPT, nicotinamide phosphoribosyltransferase; PD, Parkinson’s disease; PET, positron emission tomography; RBD, rapid eye movement sleep behavior disorder; SPECT, single photon emission tomography; TCS, transcranial sonography; UPDRS, Unified Parkinson’s Disease Rating Scales.
aStrength level, predictive value of supportive evidence [‘low’, single study/indirect evidence; ‘moderate’, >1 prospective study (patients assessed before PD developed); ‘high’, > 3 prospective studies.
bSensitivity and specificity levels (‘low’, <40%; ‘moderate’, 40%–70%; ‘high’, >70%).
cTesting cost (‘low’, evaluation by questionnaire; ‘moderate’, inexpensive; ‘high’, expensive (>$200).