The 51-year-old woman's first signs of trouble, according to her physician, were feelings of jealousy toward her husband. From this somewhat unremarkable (and possibly justified) condition followed other, more baffling personality changes, including fears that someone wanted to kill her, outbursts of loud shrieks and bouts of forgetfulness. She carried household objects back and forth, hiding them for no apparent reason. Sometimes she got lost in her own apartment. The woman's five-year decline into fullblown dementia and death, along with autopsy results, were described by her physician in a 1907 medical journal. Though insightful, his report was hardly revolutionary The physician, a German psychiatric neurologist named Alois Alzheimer, had little reason to suspect that his name would someday become a household word. But in a modern world with an unprecedented and still-growing number of elderly people, the syndrome he so carefully documented in a handful of prematurely senile patients has mushroomed into a global health crisis, affecting as many as 4 million individuals in the United States alone. Alzheimer's disease, asserts T Franklin Williams, director of the National Institute on Aging in Bethesda, Md., by far the most threatening epidemic that we have in our nation. Recent estimates suggest the disorder may affect almost half of the U.S. population aged 85 and older. It costs the nation nearly $90 billion each year and takes an immense emotional toll on its victims and their family members. Eight of the institutes and divisions within the National Institutes of Health now sponsor or conduct research on the debilitating disease. Yet after more than a decade of intensive research, scientists for the most part remain puzzled as ever. Indeed, to diagnose doctors today rely upon essentially the same behavioral and biological hallmarks described by Alzheimer himself more than 80 years ago: a progressive dementia including severe loss of memory; and the accumulation in brain tissue of protein deposits called amyloid plaques, recognizable only upon autopsy Scientists have amassed an immense amount of information too many clues, in the words of one Alzheimer's specialist about the biochemistry behind these classic symptoms. The accumulating knowledge hints that investigators may eventually solve the Alzheimer's riddle, perhaps by the end of the century, some say But daunting hurdles remain, according to Alzheimer researchers who gathered recently at the National Institutes of Health to pool their findings. Scientists at the meeting proposed causes ranging from mitochondrial mutations to unidentified, blood-borne agents, and potential cures ranging from simple aspirin to overlapping doses of potent, synthetically produced brain chemicals. Faced with a plethora of possibilities, researchers admit they simply don't know what's at the root of the disease. And with no clear idea about the fundamental differences between Alzheimer's disease and normal aging nor any reliable animal model upon which to try novel treatments they say they remain hobbled in their attempts to develop effective treatments or preventive measures. Standard treatment today is limited to antidepressants and other drugs that target secondary symptoms of the disease. In order to prevent a disease, we generally need to understand its cause. And we certainly don't know the cause of Alzheimer's, says Leon Thal, a neuroscientist at the University of California, San Diego.