PERIPHERAL MARKERS IN TESTING PATHOPHYSIOLOGICAL HYPOTHESES AND DIAGNOSING ALZHEIMERS-DISEASE

Alterations in amyloid precursor protein (APP) metabolism, calcium reg ulation, oxidative metabolism, and transduction systems have been impl icated in Alzheimer's disease (AD). Limitations to the use of postmort em brain for examining molecular mechanisms underscore the need to dev elop a human tissue model representative of the pathophysiological pro cesses that characterize AD. The use of peripheral tissues, particular ly of cultured skin fibroblasts derived from AD patients, could comple ment studies of autopsy samples and provide a useful tool with which t o investigate such dynamic processes as signal transduction systems, i onic homeostasis, oxidative metabolism, and APP processing. Peripheral cells as well as body fluids (i.e., plasma and CSF) could also provid e peripheral biological markers for the diagnosis of AD. The criteria required for a definite diagnosis of AD presently include clinical cri teria in association with histopathologic evidence obtained from biops y 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 grea t importance.