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Cerebral Zinc Metabolism in Alzheimer’s Disease

  • Craig S. Atwood
  • Robert D. Moir
  • Xudong Huang
  • Rudolph E. Tanzi
  • Ashley I. Bush
Part of the Contemporary Neuroscience book series (CNEURO)

Abstract

Most cases of Alzheimer’s disease (AD) are sporadic, and overall estimates of lifetime risk of developing AD in first-degree relatives of probands with AD suggest that only ≈50% of AD cases are influenced by hereditary risk factors (1). Meanwhile, a relatively low concordance rate of 40% in monozygotic twins (2) implicates nongenetic factors in the expression of the disease. Therefore, environmental factors could have a major impact on the pathogenesis of AD. Several environmental factors have been proposed to influence the onset of AD. However, the study of the influence of a candidate stressor on the generation of hallmark pathology of AD has been a classic approach that initially implicated aluminum exposure in the generation of neurofibrillary tangles (3,4). We have similarly explored candidate environmental or dietary factors that may impact on the deposition of Aβ as amyloid in the cerebral cortex—the other hallmark of AD neuropathology. Our approaches have been by studies of human amyloid protein precursor (APP) physiology, animal models, and in vitro models of Aβ aggregation. To date, although we have provocative data from in vivo studies, the in vitro studies of Aβ aggregation are most evolved. We have found that the solubility of the Aβ peptide is sensitively destabilized by the presence of zinc. This finding targets zinc as an important candidate environmental factor that could modulate Aβ solubility, since the brain is a unique compartment that sequesters zinc to high concentrations, whereas the blood—brain barrier in health serves to prevent undue exposure of the brain to this highly neurotoxic element.

Keywords

Amyloid Protein Precursor Zinc Homeostasis Extracellular Zinc Human Amyloid Protein Precursor Alzheimer Amyloid Precursor Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Craig S. Atwood
  • Robert D. Moir
  • Xudong Huang
  • Rudolph E. Tanzi
  • Ashley I. Bush

There are no affiliations available

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