Reduced Vascular Endothelial Growth Factor and Capillary Density in the Occipital Cortex in Dementia with L ewy Bodies

In dementia with L ewy bodies ( DLB ), blood flow tends to be reduced in the occipital cortex. We previously showed elevated activity of the endothelin and angiotensin pathways in A lzheimer'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 S er129 (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 ‐ SY 5 Y neuroblastoma cells after oxygen‐glucose deprivation ( OGD ), and VEGF level was reduced in SH ‐ SY 5 Y 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.