Alterations in amyloid precursor protein (APP) metabolism, calcium regulation, oxidative metabolism, and transduction systems have been implicated in Alzheimer's disease (AD). Limitations to the use of postmortem brain for examining molecular mechanisms underscore the need to develop a human tissue model representative of the pathophysiological processes that characterize AD. The use of peripheral tissues, particularly of cultured skin fibroblasts derived from AD patients, could complement studies of autopsy samples and provide a useful tool with which to investigate such dynamic processes as signal transduction systems, ionic homeostasis, oxidative metabolism, and APP processing. Peripheral cells as well as body fluids (i.e., plasma and CSF) could also provide peripheral biological markers for the diagnosis of AD. The criteria required for a definite diagnosis of AD presently include clinical criteria in association with histopathologic evidence obtained from biopsy or autopsy. Thus, the use of peripheral markers as a diagnostic tool, either to predict or at least to confirm a diagnosis, may be of great importance.