RESIDUES IN THE SYNUCLEIN CONSENSUS MOTIF OF THE ALPHA-SYNUCLEIN FRAGMENT, NAC, PARTICIPATE IN TRANSGLUTAMINASE-CATALYZED CROSS-LINKING TO ALZHEIMER-DISEASE AMYLOID BETA-A4 PEPTIDE

The widespread deposition of amyloid plaques is one of the hallmarks o f Alzheimer disease (AD). A recently described component of amyloid pl aques is the 35-residue peptide, non-A beta component of AD amyloid, w hich is derived from a larger intracellular neuronal constituent, alph a-synuclein. We demonstrate that transglutaminase catalyses the format ion of the covalent non-A beta component of AD amyloid polymers in vit ro as well as polymers with beta-amyloid peptide, the major constituen t of AD plaques. The transglutaminase-reactive amino acid residues in the non-A beta component of AD amyloid were identified as Gln(79) and Lys(80). Lys(80) is localized in a consensus motif Lys-Thr-Lys-Glu-Gly -Val, which is conserved in the synuclein gene family. Thus transgluta minase might be involved in the formation of insoluble amyloid deposit s and participate in the modification of other members of the synuclei n family.