Possible causes of Alzheimer's disease: Amyloid fragments, free radicals, and calcium homeostasis

Alzheimer's disease (AD) is a form of dementia in which patients develop neurodegeneration and complete loss of cognitive abilities and die prematurely. No treatment is known for this condition. Evidence points toward beta-amyloid as one of the main causes for cytotoxic processes. The cascade of biochemical events that lead to neuronal death appears to be interference with intracellular calcium homeostasis via activation of calcium channels, intracellular calcium stores, and subsequent production of free radicals by calcium-sensitive enzymes. The glutamatergic system seems to be implicated in mediating the toxic processes. Several strategies promise amelioration of neurodegenerative developments as judging from in vitro experiments. Glutamate receptor-selective drugs, antioxidants, inhibitors of nitric oxide synthase, calcium channel antagonists, receptor or enzyme inhibitors, and growth factors promise help. Especially combinations of drugs that act at different levels might prolong patients' health. (C) 1998 Academic Press.