LAMININ INHIBITS A-BETA-40 FIBRIL FORMATION PROMOTED BY APOLIPOPROTEIN E4 IN-VITRO

The aggregation of soluble A beta into insoluble amyloid fibrils is be lieved to be an important step in the pathogenesis of Alzheimer's dise ase (AD) and the prevention of this process therefore seems to be a pr omising strategy for the treatment of AD. Both apolipoprotein E(apoE) and laminin are known to play important roles in the regeneration of t he central nervous system and both are known to accumulate in the seni le plaques of the AD brains. In the present study, we therefore invest igated whether or not laminin has any effect on A beta 40 fibril forma tion promoted by apoE4 in vitro. A thioflavine-T fluorometric assay an d electron microscopic observations using negative staining together d emonstrated that laminin inhibits A beta 40 fibril formation in vitro while it also inhibits A beta 40 fibril formation promoted by apoE4. T hese results suggested that either laminin or its derivatives may thus be effective as therapeutic agents for AD. (C) 1998 Elsevier Science B.V. All rights reserved.