Metal exposure and Alzheimer’s pathogenesis
Guijian Liua, Weidong Huanga, Robert D. Moirb c, Charles R. Vanderburgb d, Barry Chi Hong Laie, Zicheng Penga, Rudolph E. Tanzib c, Jack T. Rogersc f, Xudong Huangc f✉
- aEnvironmental Science Division, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, China
- bDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
- cGenetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
- dHarvard Center for Neurodegeneration and Repair, Advanced Tissue Resource Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
- eAdvanced Photon Source, Argonne National Laboratory, Argonne, IL 60439, USA
- fNeurochemistry Laboratory, Neuroscience and Drug Discovery Unit, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
- ✉Corresponding author
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Abstract
With the growing aging population in Western countries, Alzheimer's disease (AD) has become a major public health concern. No preventive measure and effective treatment for this burdensome disease is currently available. Genetic, biochemical, and neuropathological data strongly suggest that Abeta amyloidosis, which originates from the amyloidogenic processing of a metalloprotein-amyloid precursor protein (APP), is the key event in AD pathology. However, neurochemical factors that impact upon the age-dependent cerebral Abeta amyloidogenesis are not well recognized. Growing data indicate that cerebral dysregulation of biometals, environmental metal exposure, and oxidative stress contribute to AD pathology. Herein we provided further evidence that both metals (such as Cu) and H(2)O(2) promote formation of neurotoxic Abeta oligomers. Moreover, we first demonstrated that laser capture microdissection coupled with X-ray fluorescence microscopy can be applied to determine elemental profiles (S, Fe, Cu, and Zn) in Abeta amyloid plaques. Clearly the fundamental biochemical mechanisms linking brain biometal metabolism, environmental metal exposure, and AD pathophysiology warrant further investigation. Nevertheless, the study of APP and Abeta metallobiology may identify potential targets for therapeutic intervention and/or provide diagnostic methods for AD.
TL;DRIt is demonstrated that laser capture microdissection coupled with X-ray fluorescence microscopy can be applied to determine elemental profiles (S, Fe, Cu, and Zn) in Abeta amyloid plaques and provided further evidence that both metals (such as Cu) and H(2)O( 2) promote formation of neurotoxic Abeta oligomers. (Semantic Scholar)