Neuroimaging meets neurophysiology: vascular endothelial growth factor and regional cerebral blood flow in early Alzheimer's disease.

Angiogenesis may play an important role in the pathophysiology of Alzheimer's disease (AD). Previous in vitro and in vivo studies suggest a link between angiogenesis and cerebral blood flow (CBF) in AD; however, this has never been studied clinically. In this sample of study participants with early AD (n = 15), serum vascular endothelial growth factor (VEGF), an angiogenesis biomarker, was negatively associated with regional CBF (rCBF) in the angular gyrus even after bootstrapping at a repetition of 5,000 and controlling for age, sex, and diagnosis (β = -0.015, SE = 0.006, P = 0.02, f² = 0.27, P_bootstrapped = 0.049). Sex-stratified subgroup analyses showed a strong negative correlation between rCBF in the angular gyrus and log-VEGF in males (n = 7; r = -0.78, P = 0.04), but not in females (n = 8; r = -0.16, P = 0.7). These results support an association between angiogenesis and CBF in early AD that should be further investigated in longitudinal studies and may have relevance for future therapeutic interventions in AD.NEW & NOTEWORTHY This manuscript supports the findings from previous in vitro and in vivo Alzheimer's disease (AD) studies where angiogenesis was associated with cerebral blood flow (CBF) changes. Using both neuroimaging and neurophysiology measures, this study showed the association between CBF and blood vascular endothelial growth factor (VEGF) in people with early AD, suggesting further investigation into angiogenesis and CBF as potential therapeutic targets for AD.