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Reduced vascular endothelial growth factor and capillary density in the occipital cortex in dementia with Lewy Bodies

Miners, Scott, Moulding, Hayley, de Silva, Rohan and Love, Seth 2014. Reduced vascular endothelial growth factor and capillary density in the occipital cortex in dementia with Lewy Bodies. Brain Pathology 24 (4) , pp. 334-343. 10.1111/bpa.12130

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Wiley
ISSN: 1015-6305
Date of Acceptance: 2 February 2014
Last Modified: 31 May 2019 14:36
URI: http://orca.cf.ac.uk/id/eprint/87903

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