The formation of Abeta amyloid in the human brain is considered to be the pathological hallmark of Alzheimer's Disease (AD). Recently, zinc has been discovered to induce Alzheimer's Abeta aggregation both in vitro and in the human cerebrospinal fluid (CSF) at physiological concentrations. However, the chemistry of zinc-initiated Abeta amyloid formation, as well as the neurophysiology of zinc-Abeta interaction, remains to be elucidated. The ultimate goal of this research proposal is to elucidate the chemical mechanism of zinc interaction in the context of the Abeta deposition in AD.
The specific aims of this proposal are: to characterize zinc-induced Abeta polymerization and its stoichiometry; to verify the association of abnormal zinc physiology and AD-related biochemical lesions; to identify neurochemical factors that can inhibit zinc-induced Abeta aggregation. To achieve these aims, the chemistry of zinc-Abeta interaction will be studied in vitro, and in cellular and animal systems. Also, potential mechanisms by which zinc (and copper) homeostasis may be disrupted in AD will be studied in human peripheral tissue and in cell cultures. Zinc (and copper) will be measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Abeta will be determined by ELISA and Western blotting. The chemistry and pathophysiology of zinc modulated amyloid formation will be further elucidated under this proposed study.
| Huang, Xudong; Atwood, Craig S; Moir, Robert D et al. (2004) Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Abeta peptides. J Biol Inorg Chem 9:954-60 |
| Huang, X; Cuajungco, M P; Atwood, C S et al. (2000) Alzheimer's disease, beta-amyloid protein and zinc. J Nutr 130:1488S-92S |
