We observed a highly topographically specific and consistent pattern of degeneration in the auditory system of Alzheimer's disease (AD) patients. Senile plaques (SP) and neurofibrillary tangles (NFT) were distributed throughout the ventral nucleus of the medial geniculate body (MGB) and the central nucleus of the inferior colliculus (IC) in nine of nine AD patients. Adjacent nuclei within the MGB and IC were consistently spared. NFT and SP were also present in the primary auditory and the auditory association cortices. In all control tissues, there were neither SP nor NFT in any of the above sites. The cochlear nuclei were normal in tissues from both AD and control patients. The ventral nucleus of the MGB is the major thalamic relay station for auditory function and receives fibers from neurons of the central nucleus of the IC, with projections arranged tonotopically in a laminar pattern corresponding to a gradient of high-to-low frequency ranges. The degenerative changes distributed throughout these nuclei suggest that neuronal loss may include all frequency ranges in AD. In contrast, the clinical features of presbycusis in elderly patients include only high-frequency loss due to lesions peripherally in the cochlea or auditory nerves, rather than in the central auditory nuclei. These histologic changes in the brains of AD patients may provide an additional basis for altered cognitive function due to primary sensory deafferentation.