Residues 31 to 50 carry two disease substitutions, E46K and H50Q. Both alter charge within the lipid-binding repeats, and E46K in particular changes a glutamate within a KTKEGV motif, affecting membrane association and assembly together rather than separately. This matters for how the region is interpreted. Roughly residues 30 to 55 form a convergence zone where lipid binding, intermolecular contact and aggregation propensity all overlap, which is the simplest explanation for why substitutions here produce disease while comparable changes elsewhere in the N-terminus generally do not. Genetic and biophysical evidence point at the same stretch. For antibody work the distinction that matters is between reagents recognising this mutation-dense zone and those binding elsewhere. An antibody used to detect pathology rather than total protein needs to be characterised against the region where pathology originates, and a defined peptide is how that is established. Immobilised through its long-chain biotin, this sequence also serves as a coating antigen for serological screening against the mutation region. | 