Experimental Therapeutics of Alzheimer's Disease
Brian A. Lawlor
Trinity College, Dublin
In spite of the dramatic increase in our knowledge about Alzheimer's disease (AD) over the past 25 years, the cause of this illness (or illnesses) and its exact pathogenesis still eludes us. Great advances have been made in uncovering the ultrastructure of the beta-amyloid and the neurofibrillary tangles that constitute the pathognomonic neuropathological feature of this illness; however, these great discoveries have not yet translated into meaningful developments in the therapeutics of this devastating illness. Furthermore, the absence of an animal model for AD has slowed the development of compounds that might be effective in the treatment of this illness. In spite of these drawbacks, the therapeutics of AD is an active and expanding area of research. In this chapter, the various psychopharmacological approaches that are currently being explored are reviewed, and new developments and their potential application in the next 5-10 years are discussed.
The use of agents that act on cholinergic transmission has been the mainstay of the psychopharmacological approach to the treatment of AD in the past 10-15 years. The early work of Drachman and Leavitt ( 1974) with scopolamine (a muscarinic antagonist), demonstrating that cholinergic blockade in young normals mimicked the memory loss of old age, suggested that the cholinergic system had a central role in memory. Following quickly on this finding was the report that choline acetyl transferase (ChAT), an enzyme necessary for the synthesis of acetylcholine, was decreased in the cortex of patients dying from AD