Amyloid imaging using high-field magnetic resonance.

The formation of senile plaques followed by deposition of amyloid ß peptides (Aß) are the earliest pathological changes of Alzheimer's disease (AD); thus, detection of the plaques remains the most important early diagnostic indicator of AD. Amyloid imaging is a noninvasive technique for visualizing senile plaques in the brains of patients with Alzheimer's using positron emission tomography (PET) or magnetic resonance (MR) imaging. Several types of probes have been developed for PET, but few ligands have been developed specifically for MR imaging detection of amyloid plaques. This review presents recent advances in amyloid imaging using MR imaging and includes our studies.

Relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer's disease.

Curcumin, which can exist in an equilibrium between keto and enol tautomers, binds to beta-amyloid (Abeta) fibrils/aggregates. The aim of this study was to assess the relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities. Curcumin derivatives with keto-enol tautomerism showed high levels of binding to Abeta aggregates but not to Abeta monomers. The binding activity of the keto form analogue of curcumin to Abeta aggregates was found to be much weaker than that of curcumin derivatives with keto-enol tautomerism. The color of a curcumin derivative with keto-enol tautomerism, which was substituted at the C-4 position, changed from yellow to orange within 30 min of being combined with Abeta aggregates in physiological buffer. This resulted from a remarkable increase in the enol form with extended conjugation of double bonds upon binding. These findings suggest that curcumin derivatives exist predominantly in the enol form during binding to Abeta aggregates, and that the enolization of curcumin derivatives is crucial for binding to Abeta aggregates. The keto-enol tautomerism of curcumin derivatives may be a novel target for the design of amyloid-binding agents that can be used both for therapy and for amyloid detection in Alzheimer's disease.

Trifluoromethoxy-benzylated ligands improve amyloid detection in the brain using (19)F magnetic resonance imaging.

The chemical properties of probes that improve amyloid detection by non-invasive (19)F magnetic resonance imaging (MRI) are of interest. We synthesized benzoxazole compounds with trifluoromethoxy groups, and found that these compounds displayed sharp (19)F nuclear magnetic resonance (NMR) signals in an assay buffer. However, the intensities of the (19)F NMR signals were dramatically reduced in mouse brain lysates. Our results indicate that the inhibitory effect of brain tissue on the (19)F NMR signals from these probes can be attributed to the hydrophobicity of the tissue. These results highlight the importance of using hydrophilic (19)F-MRI agents to avoid the inhibitory effects of brain tissues on (19)F NMR signals.