Metal exposure and Alzheimer's pathogenesis.
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.
Liu
Guijian
G
Environmental Science Division, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, China.
Huang
Weidong
W
Moir
Robert D
RD
Vanderburg
Charles R
CR
Lai
Barry
B
Peng
Zicheng
Z
Tanzi
Rudolph E
RE
Rogers
Jack T
JT
Huang
Xudong
X
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
C489697:APLP1 protein, human; D016564:Amyloid beta-Protein Precursor; D008670:Metals; D014131:Trace Elements