The thing Mony de Leon finds most disheartening about his job is watching healthy study volunteers develop Alzheimer disease.

A psychiatrist at New York University, de Leon is developing imaging tools and biomarkers to diagnose the debilitating disease before symptoms develop. In studies that can last 20 years, he often has to watch once-healthy individuals develop diseased brains.

Developing early diagnostic tools seemed so remote and so daunting a task that I considered it the last thing I'd do before I died.

In those afflicted with Alzheimer disease, abnormal forms of proteins called tau and amyloid-beta accumulate in the brain, and the hippocampus—the region of the brain responsible for memory—shrinks. But here's the rub: there are no clear estimates for how much of these proteins exist in a normal brain. The key to creating diagnostic tools, de Leon says, is to observe healthy people as young as age 50 and assess how these disease markers change over time. The results would help scientists set standards for comparison and start treatment early, when it is likely to be most effective.

Using data from his studies, de Leon says he can predict with 90% accuracy which individuals with mild cognitive impairment, a precursor to Alzheimer disease, will go on to develop the disease (Neurobiol. Aging 27, 394–401; 2006). He hopes to collect enough information to be able to set standards for disease markers even in healthy, young people.

When de Leon began his career in the 1970s, few scientists recognized the difference between normal aging and cognitive disease. “Developing early diagnostic tools seemed so remote and so daunting a task,” he says, “that I considered it the last thing I'd do before I died.”