Leon Thal and the therapeutic age of Alzheimer's disease

t E Alzheimer’s disease (AD) is not a degenerative condition f the aging brain about which nothing can be done (alhough such nihilism was accepted for three quarters of a entury after Alois Alzheimer’s first report); AD is a speific and treatable disease. Many, many individuals have ade important contributions to this sea change, but any in the field would agree that one person, Leon Thal, id more than any other to bring us into the therapeutic ge of AD. Leon was among a group of forward thinking scientists ho embraced the cholinergic hypothesis of AD during the ate 1970s and early 1980s. He was among the first to ranslate the hypothesis into clinical intervention, conductng both animal [1–4] and human studies. His early clinical rials in AD started with a negative study of choline [5], ollowed by positive studies of physostigmine plus lecithin 6–8] and then physostigmine alone [9]. He went on to nvestigate tacrine in rodents [10,11] and was a leader, with en Davis, of the first large-scale multicenter trial of tacrine n AD, a study that used an interesting enrichment design 12] to demonstrate the cognitive benefits of cholinesterase nhibition and was perhaps the pivotal study to launch the herapeutic age. As Leon commented on acceptance of the 004 Potamkin Prize for Research in Pick’s, Alzheimer’s, nd Related Disorders, “The importance of this trial was hat a drug was demonstrated to enhance cognition in AD nd a regulatory pathway for approval of such agents was stablished. All subsequent cholinesterase and memantine arketed have followed this same regulatory pathway [13].” pproval of tacrine by the Food and Drug Administration ccurred in 1993, and much of the pharmaceutical industry oined the effort to develop safe and effective AD treatments. From the collaborative group that conducted the first arge tacrine trial, with the encouragement of National Intitute on Aging visionaries, the Alzheimer’s Disease Co-