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

Abstract

Amyloid-β (Aβ) solution injections into an aqueous mobile phase moving through narrow bore stainless-steel capillary tubing results in adsorption of at least 99% Aβ within the tubing or injection valve. However, if flow is stopped for a period of 5–10 minutes, then started, wall desorption yields Aβ-containing molecules in the new effluent. The amount of desorbed Aβ-containing effluent depends on flow rate, period of flow cessation, and number of successive Aβ injections into the same tube without cleaning between injections. Unexpected multiple chromatographic peaks in these experiments seem to imply “separation” of released, previously adsorbed Aβ-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 Aβ 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 Aβ are injected in the same solution so that both drug and Aβ are subjected to the same shear environment. Reduction in adsorbed Aβ is suggested as an indicator of effective anti-Aβ drugs.