期刊
NEUROBIOLOGY OF AGING
卷 25, 期 10, 页码 1315-1321出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2004.01.005
关键词
Alzheimer's disease; amyloid plaque; cerebral amyloid angiopathy; Tg2576 mice; cerebrum
Metals such as zinc, copper and iron contribute to aggregation of amyloid-beta (Abeta) protein and deposition of amyloid plaques in Alzheimer's disease (AD). We examined whether the lipophilic metal chelator DP-109 inhibited these events in aged female hAbetaPP-transgenic Tg2576 mice. Daily gavage administration of DP-109 for 3 months markedly reduced the burden of amyloid plaques and the degree of cerebral amyloid angiopathy in brains, compared to animals receiving vehicle treatment. Moreover, DP-109 treatment appeared to facilitate the transition of Abeta from insoluble to soluble forms in the cerebrum. These results further support the hypothesis that endogenous metals are involved in the deposition of aggregated Abeta in brains of AD patients, and that metal chelators may be useful therapeutic agents in the treatment of AD. (C) 2004 Elsevier Inc. All rights reserved.
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