Perhaps no disorder of the human brain has aroused more interest among neuroscientists in recent years than Alzheimer’s disease (AD). This common and devastating cerebral degeneration occurs throughout the world and accounts for one-half to two-thirds of all cases of late-life intellectual failure in many developed countries that have achieved high life expectancies. The application of biochemical and molecular approaches to AD has now led to the identification of several gene products whose alterations may underlie the progressive dysfunction and dystrophy of neurons and glia that occur in the limbic and association cortices and in certain subcortical nuclei that project to them. The greatest challenge to investigators studying AD, and the greatest source of ongoing controversy, derives from attempts to place the observed morphological and biochemical changes into a temporal sequence of pathogenesis. Such efforts have been based in part on studies of young and middleaged patients with trisomy 21 (Down’s syndrome) because this disorder virtually always results in the premature development of neuropathological lesions that are indistinguishable from those of AD. The salient features of the altered biochemistry of AD brain tissue and the possible role of these changes in the pathogenesis of this complex disease are reviewed here.