New diagnostic method for Alzheimer's disease based on the toxic conformation theory of amyloid β

Recent investigations suggest that soluble oligomeric amyloid beta (A beta) species may be involved in early onset of Alzheimer's disease (AD). Using systematic proline replacement, solid-state NMR, and ESR, we identified a toxic turn at position 22 and 23 of A beta 42, the most potent neurotoxic A beta species. Through radicalization, the toxic turn can induce formation of the C-terminal hydrophobic core to obtain putative A beta 42 dimers and trimers. Synthesized dimer and trimer models showed that the C-terminal hydrophobic core plays a critical role in the formation of high molecular weight oligomers with neurotoxicity. Accordingly, an anti-toxic turn antibody (24B3) that selectively recognizes a toxic dimer model of E22P-A beta 42 was developed. Sandwich enzyme-linked immunosorbent assay with 24B3 and 82E1 detected a significantly higher ratio of A beta 42 with a toxic turn to total A beta 42 in cerebrospinal fluid of AD patients compared with controls, suggesting that 24B3 could be useful for early onset of AD diagnosis.