Last month’s Annals of Neurology had a bunch of interesting articles, so I’m going to read through them this week. Here’s the first one!
The study why: from animal models, we know that some amyloid gets broken down in the brain, but some gets transported either into the CSF, or directly through the blood-brain barrier. Which of these clearance mechanisms are important in humans was unclear.
Study design: timed arterial and venous blood samples, including from cerebral venous sinuses, were obtained from cognitively normal patients undergoing venous cerebral blood sampling anyway (to evaluate for pituitary microadenoma). 3 different assays were used, and then some quick calculations (aka “modeling”).
Results: the concentration of amyloid was increased by an average of 7.5% in central venous blood (ie blood that drains the brain) compared to arterial blood or peripheral venous blood. This was used to estimate the rate of efflux of AB peptides out of the brain (~9.7 ng/min). Using other published numbers, like the total brain turnerover of AB (18.1ng/min), the CSF reabsorption rate (0.4ml/min), the CSF AB concentration (12.4ng/cc), they estimated that about half of amyloid clearance in the human brain is via breakdown within the brain (phagocytosis by glia, proteolytic degradation) and about 25% each via the CSF and by direct transport across the BBB.
Super cool! This is my favorite kind of paper, because it a) takes actual measurements that are easy to understand, then b) does the kind of back of the envelope calculation I loved so much from physics in undergrad. Of course, there is a lot of estimating going on, but it also gives a nice, easy to remember description of how normal brains rid themselves of amyloid.