Abstract
Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r=0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker.
Highlights
Parkinson disease (PD) is the second most common neurodegenerative disease affecting an estimated 640,000 people age 65 years and over (1.6% of elders) in the United States.[1]
The 104 normal control subjects were provided locally (n = 21) and at another Parkinson’s Disease Biomarker Program (PDBP) site (n = 83), and they were age and gender matched with the PD group
The PD patients were symptomatic for 3–5 years and had United Parkinson’s Disease Rating Scale (UPDRS)-III scores from 3–50
Summary
Parkinson disease (PD) is the second most common neurodegenerative disease affecting an estimated 640,000 people age 65 years and over (1.6% of elders) in the United States.[1]. As T cells activate B cells, which make antibodies, it is not surprising that there are PD-related antibodies in the serum of PD patients.[3,4,5] The immune system may well have an important role in the progression of the disease, and immunotherapy may offer an approach to slow or stop disease progression.[6,7,8] If we could ‘read’ immune responses in such a way that they could be linked to specific disease states, a diagnostic tool of extraordinary utility would result. For disease states that are exacerbated by an immune response, if one could rapidly identify the offending antibodies and/or T-cells, and identify neutralizing molecules specific for them, a revolution in the treatment of these diseases would result
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