Metal Chelator Decreases Alzheimer β-Amyloid Plaques

five CQ-treated mice, and two showed no measurable Alzheimer ␤-Amyloid Plaques A␤ in the pellet fraction and no detectable A␤ pathology by immunocytochemistry. The authors then examined the effects of a higher dose (30 mg/kg/d) for 9 weeks in older 21-month-old mice (n ϭ 20) as compared to Transgenic mice developing ␤-amyloid (A␤) plaques sham-fed mice (n ϭ 19). This resulted in a 41% decrease are advancing experimental treatment strategies for in levels of A␤ in the brain pellet, and there was a de-Alzheimer's disease. The metal chelator, clioquinol, is crease in the immunohistochemical amyloid plaque sur-reported by Cherny et al. (2001) to reduce A␤ plaques, face area. The levels of soluble A␤ increased by 52%. presumably by chelation of A␤-associated zinc and Cerebral synaptophysin, GFAP, and APP levels were copper. This and other recent A␤-modulating treat-unchanged. The Cu and Zn levels were significantly in-ment approaches are discussed. creased in the soluble cerebral fractions of the CQ-treated mice but unchanged in the pellet. In the 21-This month's issue of Neuron contains a report of an month-old animals, CQ did not have any appreciable innovative approach to treating ␤-amyloid (A␤) deposi-effects on weight loss or mean survival, and a rating tion in a transgenic mouse model of Alzheimer's disease scale of motor activity, alertness, and general health (AD). The report by Cherny and colleagues (Cherny et indicated improvement in the CQ-treated mice as com-al., 2001 [this issue of Neuron]) builds on prior work by pared to sham control mice. this group showing that both zinc and copper in vitro These results are intriguing and suggest a possible potentiate A␤ aggregation and neurotoxicity. They also unique approach to treating A␤ deposition. There are recently reported that A␤ can bind copper and zinc and several other recently reported therapeutic approaches. may possess a superoxide dismutase activity in con-These include A␤ immunization (Schenk et al., 1999; verting O 2 to H 2 O 2. Other work has shown that copper Janus et al., 2000; Morgan et al., 2000), ␤-and ␥-secre-and zinc are elevated in the neocortex in AD and are tase inhibitors, modulators of inflammation (Lim et al., particularly concentrated in senile plaques. 2000; Wyss-Coray et al. 2001), and cholesterol-lowering With this in mind, Cherny et al. initially reported that drugs (Fassbender et al., 2001). Some of these therapies Cu/Zn chelators solubilize A␤ from postmortem AD brain are directed against cellular A␤ production and …