Abstract: Devices and methods of altering protein concentrations in cerebrospinal fluid and/or brain interstitial fluid are disclosed. Devices include a support having at least one protease attached to the support. The device may further include a housing. Devices may be implantable for use in an in vivo active flow system or for use in an in vivo passive system. Devices may also be used in an ex vivo active flow system. Devices may also be used in a passive system to treat cerebrospinal fluid and/or brain interstitial fluid that is withdrawn, or in a passive system that is implanted surgically. Methods include contacting cerebrospinal fluid and/or brain interstitial fluid with a support including at least one protease attached to the support. Proteins contained in the cerebrospinal fluid and/or brain interstitial fluid are cleaved by the protease resulting in the reduction of protein in cerebrospinal fluid and/or brain interstitial fluid.