Preliminary Capillary Flow Experiments with Amyloid-β, Possible Needle and Capillary Aβ Adsorption, and a Proposal for Drug Evaluation Under Shear Conditions.

Amyloid-beta (A beta) solution injections into an aqueous mobile phase moving through narrow bore stainless-steel capillary tubing results in adsorption of at least 99% A beta within the tubing or injection valve. However, if flow is stopped for a period of 5-10 minutes, then started, wall desorption yields A beta-containing molecules in the new effluent. The amount of desorbed A beta-containing effluent depends on flow rate, period of flow cessation, and number of successive A beta injections into the same tube without cleaning between injections. Unexpected multiple chromatographic peaks in these experiments seem to imply "separation" of released, previously adsorbed A beta-containing products in the empty capillary tubing. These preliminary experiments raise questions about possible errors in Alzheimer's disease (AD) spinal tap analyses, which use stainless-steel needles of approximately the same inner diameter and encounter similar flow rates as those in our capillary experiments. Microliter syringes and HPLC connectors also contain stainless-steel tubing that have similar inner diameter dimensions and similar flow rates. The capillary system involved in these experiments has previously been proposed as a model system for studying the effects of shear on A beta within the brain because it offers a research environment that provides highly restrictive flow through very small dimension channels. A suggestion is made for the use of this system in exploratory anti-amyloid drug studies in which both the drug and A beta are injected in the same solution so that both drug and A beta are subjected to the same shear environment. Reduction in adsorbed A beta is suggested as an indicator of effective anti-A beta drugs.