Identification of glutamine and lysine residues in Alzheimer amyloid βA4 peptide responsible for transglutaminase‐catalysed homopolymerization and cross‐linking to α2M receptor

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Abstract
The β‐amyloid peptide (βA4), derived from a larger amyloid precursor protein, is the principal component of senile plaques in Alzheimer's disease. Here we report that the full‐length (1–40) synthetic βA4 peptide, containing one glutamine and two lysine residues, is able to form homopolymers in a transglutaminase‐mediated reaction. Moreover, transglutaminase catalysed the formation of heteropolymers in reactions of βA4 with α2M receptor, a constituent of amyloid plaques, and with extracellular matrix proteins. Incorporation of site‐specific probes followed by enzymatic digestion and sequencing of tracer‐containing fractions demonstrated that both Lys16, Lys28 and Gin15 in βA4 were susceptible to cross‐linking by transglutaminase.