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.