title: Zinc overload enhances APP cleavage and Aβ deposition in the Alzheimer mouse brain.
abstract: BACKGROUND
  Abnormal zinc homeostasis is involved in β-amyloid (Aβ) plaque formation and, therefore, the zinc load is a contributing factor in Alzheimer's disease (AD). However, the involvement of zinc in amyloid precursor protein (APP) processing and Aβ deposition has not been well established in AD animal models in vivo.
  
  
  RESULTS
  In the present study, APP and presenilin 1 (PS1) double transgenic mice were treated with a high dose of zinc (20 mg/ml ZnSO4 in drinking water). This zinc treatment increased APP expression, enhanced amyloidogenic APP cleavage and Aβ deposition, and impaired spatial learning and memory in the transgenic mice. We further examined the effects of zinc overload on APP processing in SHSY-5Y cells overexpressing human APPsw. The zinc enhancement of APP expression and cleavage was further confirmed in vitro.
  
  
  CONCLUSIONS
  The present data indicate that excess zinc exposure could be a risk factor for AD pathological processes, and alteration of zinc homeostasis is a potential strategy for the prevention and treatment of AD.
authors.affiliation: Key Laboratory of Cell Biology of Ministry of Public Health, China Medical University, Shenyang, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Bao-Lu
authors.initials: BL
authors.lastname: Zhao
authors.forename: Gorm
authors.initials: G
authors.lastname: Danscher
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D006706:Homeostasis; D006801:Humans; D007858:Learning; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D053764:Presenilin-1 / Q000235:genetics; D012307:Risk Factors; D015032:Zinc / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D015032:Zinc