Table 5.
Proposed molecular biomarkers for PD diagnosis.
Type | Name | Role/Significance | Measurement | References |
---|---|---|---|---|
Biochemical biomarkers that can be investigated either in CSF or blood | Glial fibrillary acidic protein (GFAP) | This brain-specific protein and its breakdown products can serve as possible early biomarkers for PD | Detected via an in-house ELISA kit based on antibodies, with a sensitivity of concentration 70 ng/L and intra- and inter-assay coefficients of variation of 4% and 8%, respectively | [288,289] |
DJ-1 | DJ-1 expression is implicated during oxidative stress | During measuring DJ-1 content in plasma and CSF, an assessment of contamination or hemolysis of erythrocyte is required | [292] | |
Brain-derived neurotrophic factor (BDNF) | Reduced expression of BDNF within the SN serves as a potential biomarker for PD | Can be determined by ELISA | [293] | |
Neurofilament light chain protein (NFL) | Recognized in PD associated with LBs | Measuring NFL increasing levels is a very sensitive method to assess aggressive neuronal death | [294] | |
Neuromelanin | Released from dying neurons | Can be measured by MRI techniques | [295] | |
CSF α-Syn with lysosomal enzymes | The combination of CSF lysosomal enzymes, such as cathepsin and GCase in the CSF with CSF α-Syn aggregates facilitate an improved accuracy of diagnosis | Detected by protein-misfolding cyclic amplification and real-time quaking-induced conversion | [296,305] | |
miR-124 | Plasma levels of miR-124 were markedly reduced in PD patients. | Detected in plasma | [297] | |
Insulin-like growth factor 1 (IGF-1) | Potential marker for idiopathic PD in early disease stage | Detected in serum | [298] | |
Inflammatory | Fractalkine | Low levels of fractalkine associated with neuroinflammation | Detected in serum | [299] |
Neurosin | Can cleave and degrade α-Syn; decrease in neurosin levels have been reported in PD | Identified by Northern blotting/investigated in vivo using a commercial sandwich ELISA kit or a direct ELISA | [301] | |
Genetic | Mutations in SCNA, PRKN, PINK1, DJ-1, LRRK2 and GBA | Triplication of the SCNA causes a two-fold increase in α-Syn expression. | Analysis of global gene expression with DNA microarrays has been performed in the peripheral blood of PD patients | [303,304] |
CSF: cerebrospinal fluid, α-Syn: α-synuclein, ELISA: enzyme-linked immunosorbent assay, SN: substantia nigra, PD: Parkinson’s disease, miR-124: microRNA-124, PRKN: Parkin, DJ-1: Daisuke-Junko-1, LRRK2: leucine-rich repeat kinase 2, GBA: glucocerebrosidase, PINK1: PTEN-induced kinase 1.