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Amyloidogenesis induced by diet cholesterol and copper in a model mouse for Alzheimer's disease and protection effects of zinc and fluvastatin.
Brain Res Bull. 2018 10; 143:1-8.BR

Abstract

Alzheimer's disease (AD) is one of the severe chronic diseases characterized with amyloid beta (Aβ) aggregation and formation of senile-plaque (SP) like structures. Numerous risk factors including trace metals and cholesterol in diet have been identified as potential players for the onset of Aβ aggregation. To further illustrate the effects of copper and cholesterol in AD pathology, we employed an AD model mouse strain (Tg2567) and examined the histological and biochemical changes in the mouse brains and blood. When supplied with 0.1 mg/L copper in drinking water and 2% cholesterol in the food, the mice showed significant deposit of amyloid beta (Aβ) and SP plaque formation in hippocampus and temporal cortex regions in their brains. These mice also showed elevated superoxide dismutase (SOD) activity and increased ceruloplasmin (CP) concentration, and reduced glutathione peroxidase (Gpx) activity in the blood. The physiological function tests indicated these mice were significantly impeded on learning and memory. We further examined the counteracting effects of 0.1 mg/L zinc and 1.0 mg/L fluvastatin (Cholesterol-lowering drug). The combination of zinc and fluvastatin effectively reversed the copper/cholesterol caused memory loss, anatomic amyloid deposits and the biochemical changes in the blood. This work provides more evidence of high-level cholesterol and copper as risk factors to trigger amyloid aggregation and mental dementia; zinc and reduction of food cholesterol levels can protect the animals from amyloid accumulation and learning impairment. The beneficial outcomes of zinc and fluvastatin could hint some potential usages in preventive measures for high-risk AD individuals, but further rigorous test are needed.

Authors+Show Affiliations

Department of Neurology, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, 221006, China.Department of Neurology, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, 221006, China.Department of Neurology, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, 221006, China.Department of Neurology, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, 221006, China.Department of Neurology, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, 221006, China.Department of Neurology, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, 221006, China.Department of Neurology, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, 221006, China. Electronic address: mingguangwang75@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30227236

Citation

Yao, Dan, et al. "Amyloidogenesis Induced By Diet Cholesterol and Copper in a Model Mouse for Alzheimer's Disease and Protection Effects of Zinc and Fluvastatin." Brain Research Bulletin, vol. 143, 2018, pp. 1-8.
Yao D, Jing T, Niu L, et al. Amyloidogenesis induced by diet cholesterol and copper in a model mouse for Alzheimer's disease and protection effects of zinc and fluvastatin. Brain Res Bull. 2018;143:1-8.
Yao, D., Jing, T., Niu, L., Huang, X., Wang, Y., Deng, X., & Wang, M. (2018). Amyloidogenesis induced by diet cholesterol and copper in a model mouse for Alzheimer's disease and protection effects of zinc and fluvastatin. Brain Research Bulletin, 143, 1-8. https://doi.org/10.1016/j.brainresbull.2018.09.003
Yao D, et al. Amyloidogenesis Induced By Diet Cholesterol and Copper in a Model Mouse for Alzheimer's Disease and Protection Effects of Zinc and Fluvastatin. Brain Res Bull. 2018;143:1-8. PubMed PMID: 30227236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloidogenesis induced by diet cholesterol and copper in a model mouse for Alzheimer's disease and protection effects of zinc and fluvastatin. AU - Yao,Dan, AU - Jing,Tian, AU - Niu,Ling, AU - Huang,Xiuxiu, AU - Wang,Yin, AU - Deng,Xingqiang, AU - Wang,Mingguang, Y1 - 2018/09/15/ PY - 2018/06/17/received PY - 2018/09/01/revised PY - 2018/09/11/accepted PY - 2018/9/19/pubmed PY - 2019/10/1/medline PY - 2018/9/19/entrez KW - Alzheimer’s disease KW - Amyloidogenesis KW - Cholesterol KW - Copper KW - Fluvastatin KW - Zinc SP - 1 EP - 8 JF - Brain research bulletin JO - Brain Res Bull VL - 143 N2 - Alzheimer's disease (AD) is one of the severe chronic diseases characterized with amyloid beta (Aβ) aggregation and formation of senile-plaque (SP) like structures. Numerous risk factors including trace metals and cholesterol in diet have been identified as potential players for the onset of Aβ aggregation. To further illustrate the effects of copper and cholesterol in AD pathology, we employed an AD model mouse strain (Tg2567) and examined the histological and biochemical changes in the mouse brains and blood. When supplied with 0.1 mg/L copper in drinking water and 2% cholesterol in the food, the mice showed significant deposit of amyloid beta (Aβ) and SP plaque formation in hippocampus and temporal cortex regions in their brains. These mice also showed elevated superoxide dismutase (SOD) activity and increased ceruloplasmin (CP) concentration, and reduced glutathione peroxidase (Gpx) activity in the blood. The physiological function tests indicated these mice were significantly impeded on learning and memory. We further examined the counteracting effects of 0.1 mg/L zinc and 1.0 mg/L fluvastatin (Cholesterol-lowering drug). The combination of zinc and fluvastatin effectively reversed the copper/cholesterol caused memory loss, anatomic amyloid deposits and the biochemical changes in the blood. This work provides more evidence of high-level cholesterol and copper as risk factors to trigger amyloid aggregation and mental dementia; zinc and reduction of food cholesterol levels can protect the animals from amyloid accumulation and learning impairment. The beneficial outcomes of zinc and fluvastatin could hint some potential usages in preventive measures for high-risk AD individuals, but further rigorous test are needed. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/30227236/Amyloidogenesis_induced_by_diet_cholesterol_and_copper_in_a_model_mouse_for_Alzheimer's_disease_and_protection_effects_of_zinc_and_fluvastatin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(18)30448-9 DB - PRIME DP - Unbound Medicine ER -