Autoantibodies as Biomarkers of PD

Human protein microarrays were used to reveal serum autoantibodies, which are differentially expressed among PD and control subjects, and the diagnostic significance of each of these autoantibodies was evaluated, resulting in the selection of 10 autoantibody biomarkers that can effectively differentiate PD sera from control sera with a sensitivity of 93.1% and specificity of 100% (Han et al. 2012). PD sera were also distinguishable from sera obtained from AD, breast cancer, and multiple sclerosis patients with accuracies of 86.0%, 96.6%, and 100%, respectively. These results demonstrate that serum autoantibodies can be used as highly specific and accurate biomarkers for PD diagnosis throughout the course of the disease. Results of another study demonstrate that a panel of selected, blood-borne autoantibody biomarkers can distinguish early stage PD subjects from controls with an overall accuracy of 87.9%, a sensitivity of 94.1% and specificity of 85.5% (DeMarshall et al. 2015). These biomarkers were also capable of differentiating patients with

Table 14.5 Biomarkers of Parkinson disease

Serum autoantibodies

Biochemical biomarkers

  • 5-hydroxy-indole acetic acid
  • 8-hydroxy-2' deoxyguanosine increased in CSF

Mitochondrial complex I measurement

Methoxy-hydroxy-phenylethylene glycol

Vitamin D (25-hydroxyvitamin D) decreased in serum

Cardiac denervation as a biomarker of PD: shown with MIBG SPECT

Molecular biomarkers based on gene expression in blood

Imaging biomarkers

AADC (aromatic L-amino acid decarboxylase) reduction in striatum Ap identified by PET

Altered dopamine receptor binding on 11C-raclopride PET on 18F-dopa PET Dopamine transporter ligand uptake reduction on 123I p-CIT SPECT Glucose metabolism reduction in striatum on 18F-deoxyglucose PET Iron deposits in the midbrain of early PD shown by high-field MRI technology L-dopa uptake and decarboxylation reduction on 18F-dopa PET Mineral deposition in the SN on transcranial ultrasound

Peripheral benzodiazepine receptors/activated microglia on PK11195 PET, indicating neuroinflammation

VMAT2 (vesicular monoamine transporter 2) reduction on PET

Protein biomarkers: e.g., hypocretin

Screening for genetic mutations

a-synuclein gene mutations

DJ-1 oncogene for early onset PD

LRRK2 (leucine-rich repeat kinase 2) for late onset PD

NR4A2 gene mutations

Parkin

PINK-1 (PTEN Induced Putative Kinase 1)

ST13 RNA: gene expression is lower in blood of PD patients UCH-L1 (ubiquitincarboxy-terminalhydrolase L1) gene mutations

© Jain PharmaBiotech

early stage PD from those with more advanced (mild-moderate) PD with an overall accuracy of 97.5%, and could distinguish subjects with early stage PD from those with other neurological and non-neurological diseases. Serum autoantibodies are the most promising biomarkers for diagnosis of PD.

 
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