Potential Utility of Autoantibodies as Blood-Based Biomarkers for Early Detection and Diagnosis of Parkinson's Disease
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INTRODUCTION: There is a great need to identify readily accessible, blood-based biomarkers for Parkinson's disease (PD) that are useful for accurate early detection and diagnosis. This advancement would allow early patient treatment and enrollment into clinical trials, both of which would greatly facilitate the development of new therapies for PD. METHODS: Sera from a total of 398 subjects, including 103 early-stage PD subjects derived from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, were screened with human protein microarrays containing 9,486 potential antigen targets to identify autoantibodies potentially useful as biomarkers for PD. A panel of selected autoantibodies with a higher prevalence in early-stage PD was identified and tested using Random Forest for its ability to distinguish early-stage PD subjects from controls and from individuals with other neurodegenerative and non-neurodegenerative diseases. RESULTS: Results demonstrate that a panel of selected, blood-borne autoantibody biomarkers can distinguish early-stage PD subjects (90% confidence in diagnosis) from age- and sex-matched controls with an overall accuracy of 87.9%, a sensitivity of 94.1% and specificity of 85.5%. These biomarkers were also capable of differentiating patients with 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 (e.g., Alzheimer's disease and multiple sclerosis) and non-neurological (e.g., breast cancer) diseases. CONCLUSION: These results demonstrate, for the first time, that a panel of selected autoantibodies may prove to be useful as effective blood-based biomarkers for the diagnosis of early-stage PD.
DeMarshall, Cassandra; Han, Min; Nagele, Eric; Sarkar, Abhirup; Acharya, Nimish; Godsey, George; Goldwaser, Eric; Kosciuk, Mary; Thayasivam, Umashanger; Belinka, Benjamin; Nagele, Robert; and The Parkinson’s Study Group Investigators, "Potential Utility of Autoantibodies as Blood-Based Biomarkers for Early Detection and Diagnosis of Parkinson's Disease" (2015). School of Osteopathic Medicine Faculty Scholarship. 3.
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DeMarshall CA, Han M, Nagele EP, Sarkar A, Acharya NK, Godsey G, Goldwaser EL, Kosciuk M, Thayasivam U, Belinka B, Nagele RG; Parkinson’s Study Group Investigators. Potential Utility of Autoantibodies as Blood-Based Biomarkers for Early Detection and Diagnosis of Parkinson's Disease. Immunol Lett. 2015 Nov;168(1):80-8. Epub 2015 Sep 16. doi: 10.1016/j.imlet.2015.09.010. PMID: 26386375.