Table 1.
Overview of combined diagnostic and prognostic biomarkers.
| Combined biomarkers | Diagnostic value | Prognostic value | Sample size | Study | |
|---|---|---|---|---|---|
| Motor progression | Cognitive impairment | ||||
| Biofluid-based biomarkers | |||||
| Oligomeric α-synuclein/total α-synuclein in CSF | NA | Correlation with UPDRS motor (r = 0.41, P < 0.01) | NA | 121 early PD patients from the DATATOP cohort | Majbour et al. [79] |
|
Oligomeric α-synuclein/total α-synuclein, phosphorylated α-synuclein, and phosphorylated tau in CSF |
AUC 0.86, sensitivity 79%, specificity 67% | NA | NA | 46 PD patients and 48 HC | Majbour et al. [42] |
| Total tau/total α-synuclein in CSF | AUC 0.83, sensitivity 70%, specificity 88% (PD vs AD) | NA | NA | 78 PD patients and 20 AD patients | Førland et al. [80] |
| Phosphorylated tau/α-synuclein and TNF-α in CSF | AUC 0.91, sensitivity 92.9%, specificity 75% | NA | NA | 40 PD patients and 40 HC | Delgado-Alvarado et al. [81] |
| NFL, FABP3, and Aβ42 in CSF | AUC 0.87 (NFL/Aβ42) | NA | Higher NFL (P = 0.0005), lower Aβ42 (P = 0.00053), and higher FABP3 (P = 0.0037) conferred high hazard ratios for PDD | 104 PD patients and 30 HC | Bäckström et al. [82] |
| FABP3 with phosphorylated tau and total α-synuclein in CSF | AUC 0.96 (PDD vs AD) | NA | NA | 54 PD, 20 PDD, and 48 AD patients | Chiasserini et al. [83] |
| Total tau, phosphorylated tau, α-synuclein, Aβ42, NFL, MCP-1, and YKL-40 in CSF | AUC 0.95 (PD vs non-PD parkinsonism) | NA | NA | 31 PD and 94 non-PD parkinsonism patients | Magdalinou et al. [84] |
| DJ-1, total tau and phosphorylated tau | AUC 0.92, sensitivity 82%, specificity 81% (PD vs MSA) | NA | NA | 43 PD and 23 MSA patients | Herbert et al. [85] |
| Total α-synuclein, Aβ42, GCase, β-hex, and cathepsin D | AUC 0.83, sensitivity 84%, specificity 75% | NA | NA | 79 PD patients and 61 HCs from the BioFIND cohort | Parnetti et al. [86] |
| Serum TNF-α and CSF α-synuclein | AUC 0.75, sensitivity 82%, and specificity 83% | NA | NA | 12 PD patients and 6 HCs at 11 time-points across 24 h | Eidson et al. [74] |
| IFN-γ, IL-10, and TNF-α in serum | AUC 0.87, sensitivity 83%, specificity 80% | Correlation with postural instability (P < 0.001) | Correlation with cognitive impairment (P < 0.001) | 72 PD patients and 56 controls | Rathnayake et al. [87] |
| Nurr1, TNF-α, IL-1β, IL-4, IL-6, and IL-10 in PBMCs | AUC 0.71 | NA | NA | 312 PD patients, 318 HCs, and 332 NDC patients | Le et al. [73] |
| MiR-19a, miR-19b, miR-24, miR-30c, miR-34b, miR-133b, and miR-205 in CSF | AUC 0.98 | NA | NA | 28 PD patients and 28 controls | Marques et al. [88] |
| Imaging-based biomarkers | |||||
| NM-MRI and N1 imaging | AUC 0.935, sensitivity 0.85, specificity 0.92 (PD vs ET) | NA | NA | 68 PD and 25 ET patients | Jin et al. [89] |
| DAT-SPECT, DTI, and sMRI | NA | Correlation with the UPDRS (P < 0.001) | NA | 205 PD patients and 105 controls at 1-year follow-up | Lorio et al. [90] |
| NM-MRI and DAT-SPECT | AUC 0.99, sensitivity 93%, specificity 100% (PD vs non-PD parkinsonism) | NA | NA | 30 PD and 19 non-PD parkinsonism patients | Matsusue et al. [91] |
| Multiple models of combined biomarkers | |||||
| Plasma oligomer α-synuclein and multiple ESWAN imaging markers | AUC 0.827, sensitivity 0.8, specificity 0.8 | NA | NA | 60 PD patients and 30 HCs | Chen et al. [92] |
| PIGD score, caudate DAT imaging, and CSF Aβ42 | NA | Accuracy (AUC 0.684, 95% CI 0.628–0.740) in prediction of later development of FOG | NA | 393 patients with newly diagnosed PD without FOG at 4 years of follow-up | Kim et al. [93] |
| Age, CSF oligomeric/total α-synuclein, and β-glucocerebrosidase activity | AUC 0.87, sensitivity 82%, specificity 71% | NA | NA | 71 PD and 45 NDC patients | Parnetti et al. [94] |
| Age, UPSIT, RBDSQ, CSF Aβ42, and caudate DAT imaging | NA | Accuracy of prediction of cognitive impairment (AUC 0.8) | NA | 390 PD patients at 2 years of follow-up | Schrag et al. [95] |
PD, Parkinson’s disease; HC, healthy controls; AD, Alzheimer’s disease; PDD, PD dementia; ET, essential tremor; CSF, cerebrospinal fluid; AUC, area under the curve; UPDRS, Unified Parkinson’s Disease Rating Scale; NA, not analyzed; DATATOP, Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study; NFL, neurofilament light chain protein; FABP3, fatty-acid-binding protein 3; PBMCs, peripheral blood mononuclear cells; NM-MRI, neuromelanin-sensitive magnetic resonance imaging; N1, nigrosome-1; DAT-SPECT, dopamine-transporter SPECT; DTI, diffusion tensor imaging; sMRI, structural magnetic resonance imaging; ESWAN, multiple enhanced T2 star-weighted angiography; PIGD, postural instability gait difficulty; FOG, freezing of gait; UPSIT, smell identification test; RBDSQ, REM sleep behavior disorder screening questionnaire.