Environmental copper and manganese in the pathophysiology of neurologic diseases (Alzheimer's disease and manganism).

Alzheimer's disease (AD) is the most common form of dementia. Populations migrating from developing to industrialized countries seem to elicit a higher incidence and prevalence rate of AD, suggesting lifestyle and environmental factors to have a role in the pathophysiology of AD. One of its major neuropathological hallmarks is the deposition of Aβ peptides as amyloid plaques in the brain of AD patients. Aβ is proteolytically cleaved out of the larger amyloid precursor protein (APP). Cu and Mn are often found in drinking water and may have a neurotoxic potential. APP is involved in Cu homeostasis in mouse and man. In vitro observations and in vivo data obtained from APP mouse models provide strong evidence that APP overexpression enables intracellular Cu to be transported out of the cell.
Disturbed metal-ion homeostasis with elevated serum Cu levels occurs in Alzheimer and Down's patients and lowered levels in post-mortem AD brain. We observed that bioavailable Cu has specific beneficial effects in an Alzheimer's disease mouse model. This should be regarded as a proof-of-concept for a prophylactic approach to overcome the observed CNS Cu deficiency in the brain of Alzheimer's disease patients. Manganism is a disorder with symptoms similar to that of Parkinson's disease. The precise mechanism how manganese can damage the nervous system is unknown. There is some evidence that iron and manganese may utilize similar transport systems. Epidemiologic data strongly suggests that manganese enters the body primarily via inhalation and through the ingestion of manganese in drinking water.

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