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Updated: Jun 21, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Clioquinol and other hydroxyquinoline derivatives inhibit Abeta(1-42) oligomer assembly
Harry LeVine1, Qunxing Ding, John A Walker
1Department of Cellular and Molecular Biochemistry, Center on Aging, University of Kentucky, 800 S. Limestone Street, Lexington, KY 40536-0230, USA. hlevine@email.uky.edu
Abstract:
Soluble oligomeric amyloid-beta (Abeta) species are toxic to many cell types and are a putative etiological factor in Alzheimer's disease. The NINDS-Custom Collection of 1040 drugs and biologically active compounds was robotically screened for inhibitors of Abeta oligomer formation with a single-site biotinylated Abeta(1-42) oligomer assembly assay. Several quinoline-like compounds were identified with IC(50)'s <10 microM, including the antiprotozoal clioquinol that has been reported to have effects on metal ion metabolism. The 2-OH, 4-OH, and 6-OH quinolines do not block Abeta oligomer formation up to a concentration of 100 microM. Analogs of clioquinol have shown activity in reducing Abeta levels and improving behavioral deficits in mouse models of Abeta pathology. The inhibitory effects of clioquinol and other 8-OH quinoline derivatives on oligomer formation in vitro are unrelated to their chelating activity. Crosslinking studies suggest that clioquinol acts at the stage of trimer formation. These preliminary data may suggest that 8-OH quinolines have the potential for suppressing Abeta oligomer formation which should be considered when assessing the effects of these compounds in animal models and clinical trials.
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