MS approaches to investigate the role of an amyloid-beta peptide isoform in Alzheimer's plague formation onset

摘要

(i) The developed MS method of quantification of the isomerized Ab16 shows a high sensitivity (0.5 nM) that makes it a useful tool for further studies on clinical blood samples. (ii) We have found that isoA(beta)16 is hydrolyzed by N-ACE much more efficiently than the intact A(beta)16. On the basis of the obtained results it was assumed, that the N- domain of ACE can be involved in the specific degradation of the isomerized form of the beta-amyloid and thus it can influence the pathogenesis of the Alzheimer's disease. (iii) It was shown that isomerization of Asp7 residues results in Zn-induced oligomerization of A(beta), therefore, it can cause synergetic effect of zinc ions and this post-translational modification on an early molecular event of AD.