Basal Forebrain Cholinergic Neurons and Alzheimer’s Disease

Although neuropathological and epidemiological studies have long indicated Alzheimer’s dementia (AD) as a major cause of cognitive deterioration in the elderly (Larsson et al., 1963; Kay et al, 1964; Roth et al, 1967), the reports of Davies and Maloney (1976) and Bowen et al (1976) describing selective deficits in cholinergic synaptic neurochemical markers in the cortex and hippocampus of Alzheimer’s patients provoked a paradigm shift in the thinking of the neuroscientific community concerning the pathobiology of this disorder. Thus, in the 7-year period prior to these two publications, approximately 30 articles per annum appeared in the medical/scientific literature on AD, whereas in the 5-year period after these reports, the annual number of publications increased nearly 10-fold. While other factors such as the increasing interest in geriatric medicine and the growing appreciation of the social and economic implications of AD with regard to the increasing lifespan of individuals in Western society undoubtedly contributed to the burgeoning medical and scientific interest in the disorder, the discovery of selective neurotransmitter deficits in AD clearly had a tremendous impact.