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Spotting Early Indicators of Alzheimer's Disease

A molecule that binds to abnormal proteins in the brain shows promise for enabling early and reliable detection of Alzheimer's disease. The imaging molecule, known as FDDNP, may also allow scientists to assess potential new therapies to slow or halt progression of the disease.

No effective treatment yet exists for Alzheimer's disease, which affects an estimated 4.5 million Americans. Until recently, it could be definitively diagnosed only at autopsy. But researchers have long known that the brains of affected patients have accumulations of malformed proteins called amyloid and tau that create plaques and tangles. If plaques and tangles could be visualized in the living brain, Alzheimer's disease could be diagnosed earlier and potential therapies could be more effectively tested than they are now.

Dr. Gary Small and his colleagues at the University of California, Los Angeles previously developed a molecule called FDDNP that bound to plaques and tangles in brain tissue samples. In their more recent clinical study — supported by NIH's National Institute on Aging, along with other NIH components and additional funding sources — the researchers enrolled 83 adults who reported having memory problems. Participants received injections of FDDNP and underwent brain scans using positron emission tomography (PET).

Most participants received two additional types of brain scans: magnetic resonance imaging (MRI), which may show brain tissue loss, and a PET scan using a more conventional imaging molecule known as FDG, which measures brain activity. The participants took a series of thinking and memory tests as well. The tests suggested that 25 volunteers had Alzheimer's disease and 28 had mild cognitive impairment, which increases the risk of Alzheimer's disease. The remaining 30 were deemed healthy.

The scientists found that the FDDNP PET scans were more accurate than the other two imaging techniques in distinguishing among those with normal aging, those with Alzheimer's disease and those with mild cognitive impairment. Follow-up testing on a subset of the volunteers two years later showed that the FDDNP PET scans continued to match well with clinical symptoms and diagnoses. The findings were reported in the New England Journal of Medicine on December 21, 2006.

"The study suggests that we may now have a new diagnostic tool for detecting pre-Alzheimer's conditions to help us identify those at risk, perhaps years before symptoms become obvious,” Small said. “This imaging technology may also allow us to test novel drug therapies and manage disease progression over time, possibly protecting the brain before damage occurs.”