Increased cerebrospinal fluid biomarkers of angiogenesis in Parkinson’s disease.

2015

Janelidze S, Lindqvist D, Francardo V, Hall S,Zetterberg H, Blennow K, Adler CH, Beach TG, Serrano GE, van Westen D, Londos E, the Swedish BioFINDER study, Cenci A, Hansson O. Neurology, 2015 Nov 24;85(21):1834-42.

Objective: To study biomarkers of angiogenesis in Parkinson’s disease (PD), and how these are associated with clinical characteristics, blood-brain barrier (BBB) permeability, and cerebrovascular disease.

Methods: Thirty-eight elderly controls and 100 PD patients (82 without dementia and 18 with dementia) were included from the prospective Swedish BioFinder study. Cerebrospinal fluid (CSF) samples were analyzed for the angiogenesis biomarkers VEGF, PlGF, sVEGFR-1, sVEGFR-2, Ang2, and IL-8. BBB permeability, white matter lesions (WMLs) and cerebral microbleeds (CMB) were assessed. CSF angiogenesis biomarkers were also measured in two validation cohorts: (1) 64 controls and 87 PD patients with dementia; and (2) 35 controls and 93 patients with neuropathologically confirmed diagnosis of PD with and without dementia.

Results: PD patients without dementia displayed higher CSF levels of VEGF, PlGF, sVEGFR-2, and lower levels of Ang2 compared to controls. Similar alterations in VEGF, PlGF and Ang2 levels were observed in PD cases with dementia. Angiogenesis markers were associated with gait difficulties and orthostatic hypotension as well as with more pronounced BBB permeability, WMLs and CMB. Moreover, higher levels of VEGF and PlGF levels were associated with increased CSF levels of NFL (a marker of neurodegeneration) and MCP-1 (a marker of glial activation). The main results were validated in the two additional cohorts.

Conclusions: CSF biomarkers of angiogenesis are increased in PD, and they are associated with gait difficulties, BBB dysfunction, WMLs and CMB. Abnormal angiogenesis may be important in PD pathogenesis and contribute to DOPA-resistant symptoms.