Radioiodinated clioquinol as a biomarker for β-amyloid: Zn2 complexes in Alzheimer's disease

Abstract

Neocortical β-amyloid (Aβ) aggregates in Alzheimer's (AD) are enriched in transition metals that mediate assembly. Clioquinol (CQ) targets metal interaction with Aβ and inhibits amyloid pathology in transgenic mice. Here, we investigated the binding properties of radioiodinated CQ ([125I]CQ) to different in vitro and in vivo Alzheimer models. We observed saturable binding of [125I]CQ to synthetic Aβ precipitated by Zn2+ (Kd = 0.45 and 1.40 nM for Aβ1-42 and Aβ1-40, respectively), which was fully displaced by free Zn2+, Cu2+, the chelator DTPA (diethylene triamine pentaacetic acid) and partially by Congo red. Sucrose density gradient of post-mortem AD brain indicated that [125I]CQ concentrate..