Cerebrospinal Fluid (CSF)

Cerebrospinal fluid is secreted largely by the choroid plexus, circulates from the ventricles into the subarachnoid space, and drains through arachnoid granulations and along perineural and meningeal lymphatic routes. An adult holds roughly 150 millilitres at any moment and produces several hundred millilitres a day, so the whole volume turns over several times daily. Its composition is tightly controlled and unlike plasma: total protein is a small fraction of a percent of plasma protein, which is why slight blood contamination changes a result dramatically.

It matters in practice because it can be sampled by lumbar puncture in living people. That makes it the anchor for human central biomarker work, including amyloid-beta 42, phosphorylated tau and neurofilament light, and for pharmacokinetics, where a cerebrospinal-fluid-to-plasma ratio stands in for brain exposure that cannot be measured directly. Protein binding in this compartment is minimal, so the measured value is close to a free concentration, which is what makes the comparison to unbound plasma meaningful.

The decision it supports is whether a drug reached the central compartment at all, and at what fraction of plasma. A ratio of a few percent argues for a real central mechanism against a high-potency target, and against one that needs near-saturating occupancy.

The limits are routinely ignored. This fluid sits downstream of interstitial fluid behind a different barrier, so for efflux substrates it can overstate what reaches tissue. There is a rostrocaudal gradient, so lumbar values are not ventricular values, and hours can separate a plasma peak from the corresponding central peak. A traumatic tap inflates protein and peptide readings outright, and a single timepoint from a compartment with this much turnover is weak evidence for any exposure claim.