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

Alzheimer's disease (AD) is a neurodegenerative disorder that severely reduces lifespan. In this article, a new, glutamatergic denervation m odel 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 fea tures in the symptomatology of AD. In searching for neurochemical syst ems associated with the initial cognitive disorders of AD, a reorienta tion from cholinergic to glutamatergic systems is suggested. Results f rom 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 anim als indicate that major losses of glutamatergic receptors may underly the cognitive impairment seen in AD patients. A growing body of eviden ce appears to support a glutamatergic hypothesis of AD. Possible pharm acological approaches are suggested.