2004 Zenith Fellows Award

A prime suspect in Alzheimer’s disease is a tiny protein fragment, called beta-amyloid, which tends to clump together to form abnormal structures called plaques. Although beta-amyloid’s exact role in the disease is not known, it is believed to be linked to a breakdown in cell-to-cell communication and the loss of brain cells.

In early clinical trials, Ashley I. Bush, M.D., Ph.D., and his colleagues tested whether a compound called clioquinol (cleye-OCK-win-all) is an effective treatment for Alzheimer’s. Clioquinol binds to zinc and copper, two ancillary components of amyloid plaques that may act as a kind of glue. The binding of clioquinol to the metals may destabilize plaques and enable the brain to clear out beta-amyloid. The promising but somewhat mixed results from the early trials suggested the need for studies with more participants.

The researchers have also noted that clioquinol and zinc can be chemically altered to carry a radioactive label, which can be seen by certain brain imaging devices. They have hypothesized that an “amyloid label” based on clioquinol or zinc could be used to aid in early diagnosis of Alzheimer’s, track disease progression, or monitor the effect of anti-amyloid therapies.

In this research, the investigators will study clioquinol- and zinc-based labels in mice that are genetically altered to produce beta-amyloid. The researchers will assess how these labeling compounds are processed and whether they find their targets, amyloid plaques. They will also test the compounds’ targeting abilities in brain tissues from people with and without Alzheimer’s. The study outcomes may provide the foundation for further work with these compounds in clinical trials.