Anti-amyloidogenic activity of tetracyclines: studies in vitro

Cerebral deposition of beta -amyloid is a major neuropathological feature in Alzheimer's disease. Here we show that tetracyclines, tetracycline and doxycycline, classical antibiotics, exhibit anti-amyloidogenic activity. This capacity was determined by the exposure of beta 1-42 amyloid peptide to the drugs followed by the electron microscopy examination of the amyloid fibrils spontaneously formed and quantified with thioflavine T binding assay. The drugs reduced also the resistance of beta 1-42 amyloid fibrils to trypsin digestion. Tetracyclines not only inhibited the beta -amyloid aggregates formation but also disassembled the pre-formed fibrils. The results indicate that drugs with a well-known clinical profile, including activity in the central nervous system are potentially useful for Alzheimer's therapy. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.