The region 1-11 of Alzheimer amyloid-β is critical for activation of contact-kinin system

Amyloid-beta protein (A beta) has been implicated in the pathogenesis of Alzheimer's disease (AD) because of its neurotoxicity and its ability to trigger a local inflammatory response. In the present study using truncated A beta peptides, we identified the region between residues I and 11 as critical For the activation of the contact system in vitro through an ionic interaction of A beta with factor XII and/or kallikrein. Concomitant incubation of a small cationic peptide (lysine,) with A beta abrogated its ability to trigger the cleavage of high molecular weight kininogen, indicating that A beta 's activity can be blocked by an inhibitory peptide. These findings could be clinically important, since there is evidence that the contact system is activated in AD brain. Thus, prevention of contact system activation, beside diminishing the: recruitment of glial cells and microvascular permeability, can also decrease the activation of complement system and the release of IL6, both factors being considered tu play an important role in the inflammatory reactions in AD brain. (C) 2001 Elsevier Science Inc. All rights reserved.