title: Metal exposure and Alzheimer's pathogenesis.
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.
authors.affiliation: Environmental Science Division, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Guijian
authors.initials: G
authors.lastname: Liu
authors.forename: Weidong
authors.initials: W
authors.lastname: Huang
authors.forename: Robert D
authors.initials: RD
authors.lastname: Moir
authors.forename: Charles R
authors.initials: CR
authors.lastname: Vanderburg
authors.forename: Barry
authors.initials: B
authors.lastname: Lai
authors.forename: Zicheng
authors.initials: Z
authors.lastname: Peng
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Jack T
authors.initials: JT
authors.lastname: Rogers
authors.forename: Xudong
authors.initials: X
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology*; D000595:Amino Acid Sequence; D017772:Amyloid Neuropathies / Q000139:chemically induced*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D008670:Metals / Q000009:adverse effects*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D012307:Risk Factors; D014131:Trace Elements / Q000009:adverse effects
chemical_list: C489697:APLP1 protein, human; D016564:Amyloid beta-Protein Precursor; D008670:Metals; D014131:Trace Elements