Re-circulating Phagocytes Loaded with CNS Debris: A Potential Marker of Neurodegeneration in Parkinsons Disease?

Vanessa J White,Ramesh C Nayak

doi:10.3934/medsci.2015.1.26

Abstract

Diagnosis and monitoring of diseases by measurement of biochemical markers has most commonly been performed on samples of peripheral blood. However, no such markers are available for clinical use in the major diseases of the central nervous system (CNS). In Parkinson's disease circulating biomarkers would find clinical utility in early diagnosis and also monitoring of disease progression. Of particular interest is early diagnosis as this would create .a window of opportunity for treatment with neuroprotective drugs. We have developed a novel strategy for monitoring disease activity in the CNS based on the recognition that tissue injuries incite inflammation and recruitment of phagocytes that engulf debris. We postulated that some of these debris laden phagocytes may return to the peripheral blood and their cargo of CNS proteins could be measured. If CNS antigens can be measured in PBMCs it may be an indicator of active neurodegeneration as the debris engulfed by phagocytes is completely degraded within days. To make this approach more specific to Parkinson's disease we probed PBMC lysates for neuromelanin as a marker of degeneration within the substancia nigra. We performed a proof of principle study in ten subjects with early PD and ten age and sex matched controls. The biomarkers neuromelanin, Tau protein, UCH-L1 and HPCAL-1 were measured in PBMC lysates from these two groups. Neuromelanin and Tau protein mean levels were elevated in PD compared with controls and was extremely statistically significant in both cases. UCH-L1 and HPCAL-1 mean levels were elevated in PD over controls and were not quite significant in both cases. These results suggest that this is a promising new approach for diagnosis and monitoring of PD and potentially other CNS diseases.

Highlights

Parkinson’s disease (PD) is associated with a loss of neurons, in the Substantia Nigra (SN), whose neurons produce dopamine
peripheral blood mononuclear cells (PBMC) lysates of PD subjects and controls were probed for the presence of central nervous system (CNS) antigens by peptide binding assay and ELISA (Figure 2)
Hippocalcin like1 was elevated above the highest control value in 6 of 10 PD subjects (Figure 2, bottom left); p = 0.0521 (Table 2) and Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) was elevated above the highest control value in 5 of 10 PD subjects (Figure 2, bottom right); p = 0.066 (Table 2)

Summary

Introduction

PD is associated with a loss of neurons, in the Substantia Nigra (SN), whose neurons produce dopamine. Loss of dopamine results in inappropriate neuronal signaling, causing many of the clinical characteristics of PD, those related to motor function. PD is a chronic neurodegenerative disorder involving loss of neurons in various regions of the brain. It is clinically characterized by resting tremor, bradykinesia (a slowness in the execution of movement), and rigidity, often accompanied by postural instability. To facilitate neuroprotective therapies it will be necessary to identify individuals that are developing PD in a prodromal (pre-motor) phase of the disease. This would identify a window of opportunity for prevention of overt PD development

Methods

Results

Conclusion