Progress Towards In Vivo Detection of Alzheimer’s in a Live Mouse Model

Sanjeev K. Manohar, Chemical Engineering

We have 1). radiolabelled (by the Chloramine-T method of radioiodination) the Cu2+/Fe3+ metal chelator Clioquinol (CQ), which has a high affinity for the Aß peptide, with the isotope 125I, and we have 2). encapsulated 125I-CQ within small, spherical, lipophilic drug carriers (butylcyanoacrylate (BCA) nanoparticles), which are capable of crossing the blood brain barrier (BBB). We report here the biodistribution of our nanoparticle drug carriers in wildtype Swiss Webster mice, compared to the free 125I-CQ. When the radioligand is encapsulated within a drug carrier and administered intravenously to wildtype mice, the mice have an increased brain uptake of the encapsulated ligands. In vitro results show that 125I-CQ successfully labels postmortem AD brain tissue. Future work includes creating a mouse model of Alzheimer’s disease by direct stereotaxic injections of aggregated Aß (1,40) peptide into the CA1 hippocampal region. Preliminary stereotaxic injections and baseline behavioral Y-maze testing have been preformed. The implication of our research is that in vivo imaging would be a breakthrough in the diagnosis of early AD.