title: High manganese, a risk for Alzheimer's disease: high manganese induces amyloid-β related cognitive impairment.
abstract: Excess manganese (Mn) in brain can be neurotoxic, implicated in several neurodegenerative disorders such as sporadic Alzheimer's disease (AD). However, little is known about the altered metal environment including elevated Mn in the progressive cognitive impairment of AD. Indeed, whether high Mn is associated with AD risk remains elusive. In the study, we recruited 40 Chinese elders with different cognitive statuses and investigated concentrations of Mn in whole blood and plasma amyloid-β (Aβ) peptides. Surprisingly, there were significant correlations of Mn with Mini-Mental State Examination score and Clinical Dementia Rating Scale score. In addition, plasma Aβ peptides increased with elevated Mn. Further studies both in vitro and in vivo demonstrated dose-related neurotoxicity and increase of Aβ by Mn treatment, which was probably caused by disrupted Aβ degradation. These data suggested that high Mn may be involved in the progress of AD as an essential pathogenic factor.
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Yawei
authors: Y
authors: Tong
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Huan
authors: H
authors: Yang
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Xiaosheng
authors: X
authors: Tian
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Hecheng
authors: H
authors: Wang
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Ting
authors: T
authors: Zhou
authors: Beijing Geriatric Hospital, Beijing, China.
authors: Shouzi
authors: S
authors: Zhang
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China Beijing Geriatric Hospital, Beijing, China.
authors: Jia
authors: J
authors: Yu
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Tao
authors: T
authors: Zhang
authors: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors: Dongshen
authors: D
authors: Fan
authors: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors: Xiangyang
authors: X
authors: Guo
authors: Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Tabira
authors: Affiliated Rehabilitation Hospital of National Research Center for Rehabilitation Technical Aids, Beijing, China.
authors: Fanjun
authors: F
authors: Kong
authors: Beijing Geriatric Hospital, Beijing, China.
authors: Zheng
authors: Z
authors: Chen
authors: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors: Weizhong
authors: W
authors: Xiao
authors: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China Department of Neurology, Peking University Third Hospital, Beijing, China.
authors: Dehua
authors: D
authors: Chui
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000009:adverse effects* / Q000378:metabolism*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008609:Mental Status Schedule; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D008345:Manganese; D007770:L-Lactate Dehydrogenase
keywords: Alzheimer's disease (AD); Aβ degradation; High manganese (Mn); amyloid-beta (Abeta); cognitive impairment