Janelidze Shorena, Lindqvist Daniel, Francardo Veronica, Hall Sara, Zetterberg Henrik, Blennow Kaj, Adler Charles H, Beach Thomas G, Serrano Geidy E, van Westen Danielle, Londos Elisabet, Cenci M Angela, Hansson Oskar
From the Clinical Memory Research Unit, Department of Clinical Sciences (S.J., E.L., O.H.), Lund University, Malmö; the Department of Clinical Sciences (D.L., S.H.), Division of Psychiatry (D.L.), Department of Experimental Medical Science (V.F., M.A.C.), and Clinical Sciences, Diagnostic Radiology (D.v.W.), Lund University, Lund; Psychiatry Skåne (D.L.), Lund; the Department of Neurology (S.H.) and Memory Clinic (E.L., O.H.), Skåne University Hospital, Lund; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), London, UK; The Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences (K.B.), Stockholm, Sweden; Department of Neurology (C.H.A.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B., G.E.S.), Sun City, AZ; and Imaging and Function (D.v.W.), Skåne University Health Care, Lund, Sweden.
Neurology. 2015 Nov 24;85(21):1834-42. doi: 10.1212/WNL.0000000000002151. Epub 2015 Oct 28.
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.
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.
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.
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.
研究帕金森病（PD）中血管生成的生物标志物，以及这些标志物与临床特征、血脑屏障（BBB）通透性和脑血管疾病之间的关系。
在这项横断面分析中，从瑞典前瞻性BioFinder研究中纳入了38名老年对照者和100名PD患者（82名无痴呆症患者和18名有痴呆症患者）。对脑脊液样本进行分析，检测血管生成生物标志物血管内皮生长因子（VEGF）、其受体VEGFR-1和VEGFR-2、胎盘生长因子（PlGF）、血管生成素2（Ang2）和白细胞介素-8。评估BBB通透性、白质病变（WMLs）和脑微出血（CMB）。还在2个验证队列中测量了脑脊液血管生成生物标志物：（1）64名对照者和87名患有痴呆症的PD患者；（2）35名对照者和93名经神经病理学确诊为有或无痴呆症的PD患者。
与对照组相比，无痴呆症的PD患者脑脊液中VEGF、PlGF和sVEGFR-2水平较高，而Ang2水平较低。在患有痴呆症的PD患者中也观察到VEGF、PlGF和Ang2水平有类似变化。血管生成标志物与步态困难、体位性低血压以及更明显的BBB通透性、WMLs和CMB有关。此外，较高的VEGF和PlGF水平与脑脊液中神经丝轻链（神经退行性变的标志物）和单核细胞趋化蛋白-1（神经胶质激活的标志物）水平升高有关。主要结果在另外2个队列中得到验证。
PD患者脑脊液中的血管生成生物标志物升高，且与步态困难、BBB功能障碍、WMLs和CMB有关。异常血管生成可能在PD发病机制中起重要作用，并导致对多巴耐药的症状。
