Choroid Plexus-CSF Homeostatic Systems

Disruption of Choroid Plexus-CSF Homeostatic Systems in Aging and Alzheimer’s Disease

IHRF Scientific Advisor and this year’s NHD Symposium keynote speaker Conrad Johanson, Ph.D. brought the research conference to a close with a discussion about the consequences of a decrease in CSF production with aging. Dr. Johanson believes that reduced CSF formation leads to a disruption in CSF flow dynamics and reduced CSF turnover, which, in turn, allows for damaging toxins, like beta amyloid, to accrue in the brain.

CSF formation in humans, as well as animals, decreases by 50% or more in the late stages of life. This occurs as a result of the diminishing expression of Na-K-ATPase, carbonic anhydrase and aquaporins in the choroid epithelium.
A breakdown in the choroid plexus secretory systems also occurs with aging. Choroidal fluid generation is critical to extracellular fluid balance in the central nervous system, and is necessary to maintain CSF volume, pressure and chemical composition. Actual examination of the choroid plexus has shown physical changes including calcifi cation, immune complex deposition and interstitial fibrosis, all of which lead to less eff ective transfer of solutes across the blood-CSF barrier.

In addition, Dr. Johanson reported that lower CSF turnover that occurs with aging means that essential nutrients are not supplied efficiently to neurons while potentially harmful, plaque-like substances known as catabolites are slowly and
ineffectually removed. (Beta amyloid is a catabolite that has been associated with Alzheimer’s disease.)

This aging-induced disruption in CSF dynamics likely contributes to the exacerbation of dementias such as Alzheimer’s disease (AD). Dr. Johanson discovered that in severe AD, certain proteins involved in homeostatic regulation had been upregulated. The fluid regulator NA-K-Cl co-transporter in the apical membrane of the choroid plexus was also found at a higher expression level.

Dr. Johanson suggested that enhanced reabsorptive activity of the Na-K-Cl cotransporter is associated with the slowing of CSF production. The development of drugs to increase or regulate CSF formation may help to solve the problems associated with altered CSF flow dynamics.