Anti-amyloidogenic activity of tetracyclines: Studies in vitro

Abstract

Cerebral deposition of β-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 β 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 β 1-42 amyloid fibrils to trypsin digestion. Tetracyclines not only inhibited the β-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. © 2001 Federation of European Biochemical Societies.