Abstract
Objective: To study biomarkers of angiogenesis in Parkinson disease (PD), and how these are associated with clinical characteristics, blood–brain barrier (BBB) permeability, and cerebrovascular disease.
Methods: In this cross-sectional analysis, 38 elderly controls and 100 patients with PD (82 without dementia and 18 with dementia) were included from the prospective Swedish BioFinder study. CSF samples were analyzed for the angiogenesis biomarkers vascular endothelial growth factor (VEGF); its receptors, VEGFR-1 and VEGFR-2; placental growth factor (PlGF); angiopoietin 2 (Ang2); and interleukin-8. BBB permeability, white matter lesions (WMLs), and cerebral microbleeds (CMB) were assessed. CSF angiogenesis biomarkers were also measured in 2 validation cohorts: (1) 64 controls and 87 patients with PD with dementia; and (2) 35 controls and 93 patients with neuropathologically confirmed diagnosis of PD with and without dementia.
Results: Patients with PD without dementia displayed higher CSF levels of VEGF, PlGF, and sVEGFR-2, and lower levels of Ang2, compared to controls. Similar alterations in VEGF, PlGF, and Ang2 levels were observed in patients with PD 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 neurofilament light (a marker of neurodegeneration) and monocyte chemotactic protein–1 (a marker of glial activation). The main results were validated in the 2 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.
GLOSSARY
- Aβ=
- β-amyloid;
- Ang=
- angiopoietin;
- ARWMC=
- age-related white matter changes;
- BBB=
- blood–brain barrier;
- CMB=
- cerebral microbleeds;
- CV=
- coefficient of variation;
- DLB=
- dementia with Lewy bodies;
- IL=
- interleukin;
- MCP-1=
- monocyte chemotactic protein–1;
- NFL=
- neurofilament light;
- p-tau=
- phospho-tau;
- PD=
- Parkinson disease;
- PDD=
- Parkinson disease with dementia;
- PDND=
- Parkinson disease without dementia;
- PlGF=
- placental growth factor;
- SNpc=
- substantia nigra pars compacta;
- t-tau=
- total tau;
- VEGF=
- vascular endothelial growth factor;
- WML=
- white matter lesions
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by Lund University, Sweden, with funding from the European Research Council.
Supplemental data at Neurology.org
Editorial, page 1826
- Received March 25, 2015.
- Accepted in final form July 9, 2015.
- © 2015 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
Letters: Rapid online correspondence
- Author response: Blood-CSF barrier dysfunction may affect CSF levels of angiogenesis in PD
- Blood-CSF barrier dysfunction may affect CSF levels of angiogenesis in PD
- Author Response: The role of neuro-inflammation in Parkinson Disease
- The role of neuro-inflammation in Parkinson Disease
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