ANIMAL-MODELS OF ALZHEIMERS-DISEASE - GLUTAMATERGIC DENERVATION AS AN ALTERNATIVE APPROACH TO CHOLINERGIC DENERVATION

Alzheimer's disease (AD) is a neurodegenerative disorder that severely reduces lifespan. In this article, a new, glutamatergic denervation model of AD is presented as a supplement to the well known cholinergic one, because these models are trying to mimic different aspects of the pathology in AD. Impaired memory and disorientation are prominent features in the symptomatology of AD. In searching for neurochemical systems associated with the initial cognitive disorders of AD, a reorientation from cholinergic to glutamatergic systems is suggested. Results from recent behavioral studies of damage to the temporal and entorhinal cortices in rats imply that these structures are strongly involved in mnemonic function. Findings from Alzheimer brains and laboratory animals indicate that major losses of glutamatergic receptors may underly the cognitive impairment seen in AD patients. A growing body of evidence appears to support a glutamatergic hypothesis of AD. Possible pharmacological approaches are suggested.