Adverse psychological impact, glutamatergic dysfunction, and risk factors for Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cell loss and pathological changes in neuronal transmission. In particular, malfunction in glutamatergic activity may be associated with the impairment of memory seen in Alzheimer patients. Both hypoactivation and hyperactivation of glutamatergic systems seem to cause impeded cognitive processing in animals. Rats subjected to rearing in isolation display reduced levels of glutamate in temporal regions accompanied by impaired learning and memory. Similar cognitive deficits are also seen in animals exposed to behavioral stress. Stress appears to have deleterious effects on cognition caused by glutamate neurotoxicity leading to attenuated synaptic activity. It is suggested that stress may represent a potential risk factor for AD. The known risk factors for AD (age, heredity, head trauma, low education, depression) may all be related to glutamatergic dysfunction. Some difficulties with pharmacological approaches based on glutamatergic agonists are discussed. It is suggested that optimal glutamate-mediated neurotransmission throughout life may prevent the occurrence of mental decline associated with AD. (C) 1998 Elsevier Science Ltd. All rights reserved.