title: Reduced vascular endothelial growth factor and capillary density in the occipital cortex in dementia with Lewy bodies.
abstract: In dementia with Lewy bodies (DLB), blood flow tends to be reduced in the occipital cortex. We previously showed elevated activity of the endothelin and angiotensin pathways in Alzheimer's disease (AD). We have measured endothelin-1 (ET-1) level and angiotensin-converting enzyme (ACE) activity in the occipital cortex in DLB and control brains. We also measured vascular endothelial growth factor (VEGF); factor VIII-related antigen (FVIIIRA) to indicate microvessel density; myelin-associated glycoprotein (MAG), a marker of ante-mortem hypoperfusion; total α-synuclein (α-syn) and α-synuclein phosphorylated at Ser129 (α-syn-p129). In contrast to findings in AD, ACE activity and ET-1 level were unchanged in DLB compared with controls. VEGF and FVIIIRA levels were, however, significantly lower in DLB. VEGF correlated positively with MAG concentration (in keeping with a relationship between reduction in VEGF and hypoperfusion), and negatively with α-syn and α-syn-p129 levels. Both α-syn and α-syn-p129 levels increased in human SH-SY5Y neuroblastoma cells after oxygen-glucose deprivation (OGD), and VEGF level was reduced in SH-SY5Y cells overexpressing α-syn. Taken together, our findings suggest that reduced microvessel density rather than vasoconstriction is responsible for lower occipital blood flow in DLB, and that the loss of microvessels may result from VEGF deficiency, possible secondary to the accumulation of α-syn.
authors: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors: Scott
authors: S
authors: Miners
authors: Hayley
authors: H
authors: Moulding
authors: Rohan
authors: R
authors: de Silva
authors: Seth
authors: S
authors: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002196:Capillaries / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D016228:Endothelial Growth Factors / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000172:deficiency; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009778:Occipital Lobe / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010766:Phosphorylation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D016228:Endothelial Growth Factors; D019332:Endothelin-1; C115082:MAG protein, human; D018992:Myelin-Associated Glycoprotein; C497604:SNCA protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051844:alpha-Synuclein; D014841:von Willebrand Factor; D007703:Peptidyl-Dipeptidase A; D005947:Glucose
keywords: VEGF; dementia with Lewy bodies; factor VIII-related antigen; hypoperfusion; oxygen-gluocose deprivation