Characterisation of the binding of amyloid imaging tracers to rodent Aβ fibrils and rodent-human Aβ co-polymers

Despite the application of amyloid imaging agents such as PIB, SB13, and FDDNP in Alzheimer’s disease (AD) patients, the successful use of these agents in transgenic mice models of AD has not been reported to date. As a first step in understanding the behaviour of these ligands in transgenic models of AD, we have investigated in a series of in vitro ligand binding assays the interaction of selected agents, including PIB, FDDNP, SB13, and BSB, with amyloid fibrils produced from rodent Aβ(1–40) (roAβ) peptide. The data indicate that the ligand binding affinities together with the pattern and number of binding sites on the roAβ fibrils are broadly conserved with that reported previously for human Aβ(1–40) (huAβ) fibrils. However, characterisation of huAβ fibrils formed in the presence of increasing amounts of roAβ (1, 5, 10% w/w) demonstrated a dose-dependent reduction in the number of high affinity [3H]Me-BTA-1 binding sites such that at the highest amount of roAβ the specific signal was reduced by ∼95%. These studies suggest that (i) the presence of small amounts of roAβ in huAβ fibrils has the potential to cause subtle ultrastructural alterations in the polymers and (ii) the weak binding signal observed in vivo in the transgenic mouse models of AD may in part be due to the decreased number of high affinity binding sites on the Aβ fibrils.