Cerebral venous biomarkers and veno-arterial gradients: untapped resources in Alzheimer's disease

Blood based biomarkers (BBB) derived from forearm veins for estimating brain changes is becoming ubiquitous in Alzheimer's Disease (AD) research and could soon become standard in routine clinical diagnosis. However, there are many peripheral sources of contamination through which concentrations of these metabolites can be raised or lowered after leaving the brain and entering the central venous pool. This raises the issue of potential false conclusions that could lead to erroneous diagnosis or research findings. We propose the use of simultaneous sampling of internal jugular venous and arterial blood to calculate veno-arterial gradient, which can reveal either a surplus or a deficit of metabolites exiting the brain. Methods for sampling internal jugular venous and arterial blood are described along with examples of the use of the veno-arterial gradient in non-AD brain research. Such methods in turn could help better establish the accuracy of forearm venous biomarkers.