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

Amyloid-beta protein (A beta) has been implicated in the pathogenesis of Al zheimer's disease (AD) because of its neurotoxicity and its ability to trig ger a local inflammatory response. In the present study using truncated A b eta peptides, we identified the region between residues I and 11 as critica l For the activation of the contact system in vitro through an ionic intera ction of A beta with factor XII and/or kallikrein. Concomitant incubation o f a small cationic peptide (lysine,) with A beta abrogated its ability to t rigger the cleavage of high molecular weight kininogen, indicating that A b eta 's activity can be blocked by an inhibitory peptide. These findings cou ld be clinically important, since there is evidence that the contact system is activated in AD brain. Thus, prevention of contact system activation, b eside diminishing the: recruitment of glial cells and microvascular permeab ility, can also decrease the activation of complement system and the releas e of IL6, both factors being considered tu play an important role in the in flammatory reactions in AD brain. (C) 2001 Elsevier Science Inc. All rights reserved.