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Metals and amyloid-? in Alzheimer's disease *

Mounting evidence is demonstrating roles for the amyloid precursor protein (APP) and its proteolytic product Aβ in metal homeostasis. Furthermore, aberrant metal homeostasis is observed in patients with Alzheimer's disease (AD), and this may contribute to AD pathogenesis, by enhancing the formation of reactive oxygen species and toxic Aβ oligomers and facilitating the formation of the hallmark amyloid deposits in AD brain.

 Indeed, zinc released from synaptic activity has been shown to induce parenchymal and cerebrovascular amyloid in transgenic mice. On the other hand, abnormal metabolism of APP and Aβ may impair brain metal homeostasis as part of the AD pathogenic process. Aβ and APP expression have both been shown to decrease brain copper (Cu) levels, whereas increasing brain Cu availability results in decreased levels of Aβ and amyloid plaque formation in transgenic mice.

 Lowering Cu concentrations can downregulate the transcription of APP, strengthening the hypothesis that APP and Aβ form part of the Cu homeostatic machinery in the brain. This is a complex pathway, and it appears that when the sensitive metal balance in the brain is sufficiently disrupted, it can lead to the self-perpetuating pathogenesis of AD. Clinical trials are currently studying agents that can remedy abnormal Aβ–metal interactions.

* Legal Disclaimer: Chelation and Hyperbaric Therapy, Stem Cell Therapy, and other treatments and modalities mentioned or referred to in this web site are medical techniques that may or may not be considered “mainstream”. As with any medical treatment, results will vary among individuals, and there is no implication or guarantee that you will heal or achieve the same outcome as patients herein.

As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 04-07-2008