Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease

^a I.R.C.C.S San Giovanni di Dio, Alzheimer's Disease Unit Sacred Heart Hospital-FBF, Brescia
^b Department of Experimental Medicine and Biochemical Sciences, University of Roma Tor Vergata
^c Internal Medicine Department, Geriatric Clinic, University of Pavia, Italy
^d Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
^e Institute for Cognitive and Computational Sciences, Georgetown University Medical Center, Washington D.C. 20007, USA
^f Cornell University Medical College at Burke Medical Research Institute, New York 10605, USA
^g Institute of Pharmacological Sciences, University of Milano
^h University of Pavia, Italy

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.—Gasparini, L., Racchi, M., Binetti, G., Trabucchi, M., Solerte, S. B., Alkon, D., Etcheberrigaray, R., Gibson, G., Blass, J., Paoletti, R., Govoni, S. Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease. FASEB J. 12, 17–34 (1998)

Key Words: peripheral cells • CSF • plasma • diagnosis

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