TY - JOUR
T1 - The distribution profile and oxidation states of biometals in APP transgenic mouse brain
T2 - Dyshomeostasis with age and as a function of the development of Alzheimer's disease
AU - Wang, Huajian
AU - Wang, Meng
AU - Wang, Bing
AU - Li, Ming
AU - Chen, Hanqing
AU - Yu, Xiaohan
AU - Zhao, Yuliang
AU - Feng, Weiyue
AU - Chai, Zhifang
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/3
Y1 - 2012/3
N2 - The enrichment of transition metals in the brain and the dyshomeostasis of metals are thought to be important etiological factors for elderly people in a number of neurodegenerative diseases, including Alzheimer's disease (AD). However, the understanding of how biometals dynamically dysregulate in the stages of AD development, such as the exact time-dependent and site-dependent accumulation in the brain with AD progression, is still limited. Herein, by using the APP/V717I transgenic mouse model and age-matched mice as control, we offer distinctive in situ and quantitative images of metals (Cu, Fe, Zn and Ca) in brain sections by synchrotron radiation micro beam X-ray fluorescence (SR-μXRF). The images show that Fe and Ca increased with brain aging in both AD and control (CNT) mice, and Cu, Fe, Zn and Ca appeared significantly elevated in AD mice and showed an obvious age-dependent rise. Fe, Cu and Zn were obviously specifically enriched in the cortex and hippocampus, which were also the plaque-formation sensitive brain regions. Our results demonstrate that the enrichment of transition metals with age and metals' dyshomeostasis in specific regions may contribute together to the etiology and development of AD in elderly people. The XANES measurements of Cu and Fe show evidence that Cu may have redox properties in the AD brain.
AB - The enrichment of transition metals in the brain and the dyshomeostasis of metals are thought to be important etiological factors for elderly people in a number of neurodegenerative diseases, including Alzheimer's disease (AD). However, the understanding of how biometals dynamically dysregulate in the stages of AD development, such as the exact time-dependent and site-dependent accumulation in the brain with AD progression, is still limited. Herein, by using the APP/V717I transgenic mouse model and age-matched mice as control, we offer distinctive in situ and quantitative images of metals (Cu, Fe, Zn and Ca) in brain sections by synchrotron radiation micro beam X-ray fluorescence (SR-μXRF). The images show that Fe and Ca increased with brain aging in both AD and control (CNT) mice, and Cu, Fe, Zn and Ca appeared significantly elevated in AD mice and showed an obvious age-dependent rise. Fe, Cu and Zn were obviously specifically enriched in the cortex and hippocampus, which were also the plaque-formation sensitive brain regions. Our results demonstrate that the enrichment of transition metals with age and metals' dyshomeostasis in specific regions may contribute together to the etiology and development of AD in elderly people. The XANES measurements of Cu and Fe show evidence that Cu may have redox properties in the AD brain.
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U2 - 10.1039/c2mt00104g
DO - 10.1039/c2mt00104g
M3 - Article
C2 - 22301945
AN - SCOPUS:84863237053
SN - 1756-5901
VL - 4
SP - 289
EP - 296
JO - Metallomics
JF - Metallomics
IS - 3
ER -