Alzheimer's disease: fundamental and therapeutic aspects

Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early--as well as late--onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid beta-protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease.