Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease

Abstract

Background Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. There is increasing evidence that PD pathology is accompanied by an inflammatory response. This is highly relevant for understanding disease progression and the development of novel neuroprotective therapies. Objective Assessing potential dysregulation of a panel of inflammatory mediators in the peripheral blood mononuclear cells (PBMCs) and plasma of PD patients and in the context of clinical outcome metrics. Methods We performed a screening of selected cell-surface chemokine receptors and adhesion molecules in PBMCs from PD patients and age-matched healthy controls in a flow cytometry-based assay. ELISA was used to quantify VCAM1 levels in the plasma of PD patients. Lymphocytic chemotactic ability was assessed using a modified Boyden chamber assay. Results VLA4 expression was significantly downregulated on CD3+ T cells, CD56+ NK cells, and CD3+/CD56+ NK-T cells from PD patients; further, an increase of the soluble VLA4 ligand VCAM1 in patient plasma was noted. sVCAM1 in PD patients was even higher than reported for patients with multiple sclerosis, neuromyelitis optica, and rheumatoid arthritis. sVCAM1 levels correlated with the disease stage (Hoehn and Yahr scale) and motor impairment. Chemoattraction with SDF-1α revealed impaired motility of lymphocytes from PD patients relative to controls. Conclusion Our data provides evidence for a functional dysregulation of the sVCAM1-VLA4 axis in PD. Further studies evaluating the therapeutic potential of this axis are warranted. Electronic supplementary material The online version of this article (10.1186/s12974-019-1482-8) contains supplementary material, which is available to authorized users.

Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier

“…Moreover, they can be found in acute disseminated encephalomyelitis, which is a postinfectious inflammatory disease, and in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis, where their level correlates with disease severity (70). Similar observations were made in patients suffering from Parkinson's disease (71), highlighting the potential relation between sCAM levels in biological fluids and inflammation. Interestingly, an increase in soluble VCAM-1 has been detected in severe DENV infections and was proposed to represent a marker to monitor disease severity (72).…”

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“…Under these conditions, they contribute to the recruitment of circulating blood cells into the brain microvasculature via the expression of adhesion molecules [ 79 ]. Interestingly, high levels of soluble VCAM1 were reported in plasma from PD patients when compared to age-matched controls, that correlated with disease stage and motor impairment [ 81 ], indicating strong blood–brain connections through cell traffic.…”

Endothelial C3a receptor mediates vascular inflammation and blood-brain barrier permeability during aging

“…Furthermore, evidence that vascular inflammation, marked by increased endothelial expression of vascular cell adhesion molecule VCAM1, stokes CNS aging by decreasing neural stem cell number and increasing microglial reactivity has been reported (11). Elevated levels of VCAM1 have also been found to correlate with Parkinson's disease severity (12) and, recently, lymphocytes known to bind VCAM1 in brain vasculature were found in aged and AD patient brains (13,14). Single-cell transcriptomic analysis of hippocampal brain endothelial cells (BECs) has shown that age-related changes in these cells are rooted in responses to innate inflammatory cues, hypoxic stimuli, and oxidative stress (15).…”