Doxycycline prevents amyloid deposition in vivo and directly interacts with LC in vitro. (A) In control CMV-λ6 transgenic mice drinking water alone, 69% (11/16) had Congo red positive deposits in the stomach. (B) Deposits were inhibited by oral administration of doxycycline in the drinking water, identified in only 23% (4/17) of the treated mice (P = .00006, χ2 analysis). (C) For a 5-day period of incubation, recombinant amyloidogenic LC in vitro form typical amyloid fibrils, as visualized by negative stain TEM, (D) whereas incubation with 250 mg/L doxycycline resulted in degraded and broken fibrils and disorganized bundles of immature fibrils (data not shown). (E) With 15 mg/L doxycycline, broken fibrils with frayed ends were observed. (F) Amyloid fibrils extracted from autopsy material formed numerous large aggregates after incubation with doxycycline. (C-E) Magnification ×42 000, bar = 100 nm; magnification ×10 000, bar = 500 nm.
