Analysis of Amyloid Beta 1-16 (Aβ16) Monomer and Dimer Using Electrospray Ionization Mass Spectrometry with Collision-Induced Dissociation

The monomer and dimer structures of the amyloid fragment Aβ(1-16) sequence formed in H₂O were investigated using electrospray ionization mass spectrometry (MS) and tandem MS (MS/MS). Aβ16 monomers and dimers were indicated by signals representing multiple proton adduct forms, [monomer+zH]ⁿ⁺ (=M^z+, z = charge state) and [dimer+zH]^z+ (=D^z+), in the MS spectrum. Fragment ions of monomers and dimers were observed using collision-induced dissociation MS/MS. Peptide bond dissociation was mostly observed in the D1-D7 and V11-K16 regions of the MS/MS spectra for the monomer (or dimer), regardless of the monomer (or dimer) charge state. Both covalent and non-covalent bond dissociation processes were indicated by the MS/MS results for the dimers. During the non-covalent bond dissociation process, the D³⁺ dimer complex was separated into two components: the M¹⁺ and M²⁺ subunits. During the covalent bond dissociation of the D³⁺ dimer complex, the b and y fragment ions attached to the monomer, (M+b_10-15)^z+ and (M+y_9-15)^z+, were thought to originate from the dissociation of the M²⁺ monomer component of the (M¹⁺+M²⁺) complex. Two different D³⁺ complex geometries exist; two distinguished interaction geometries resulting from interactions between the M¹⁺ monomer and two different regions of M²⁺ (the N-terminus and C-terminus) are proposed. Intricate fragmentation patterns were observed in the MS/MS spectrum of the D⁵⁺ complex. The complicated nature of the MS/MS spectrum is attributable to the coexistence of two D⁵⁺ configurations, (M¹⁺+M⁴⁺) and (M²⁺M³⁺), in the Aβ16 solution.