Alzheimer's Unlocking the Mystery: The Longer We Live, the More Likely We Are to Contract This Devastating Disease. but Recent Discoveries Are Bringing Scientists Closer Than Ever to a Cure

Article excerpt

The fog, as Carl Sandburg said, comes on little cat feet. First you notice that you're always misplacing things, or that common nouns are evading you as stubbornly as the names of new acquaintances. Pretty soon you're forgetting appointments and getting flustered when you drive in traffic. On bad days you find you can't hold numbers in your mind long enough to dial the phone. You try valiantly to conceal your lapses, but they become ever more glaring. You crash your car. You spend whole mornings struggling to dress yourself properly. And even as you lose the ability to read or play the piano, you're painfully aware of what's happening to you. Then the fog thickens. Your own children come to look like strangers, and terrifying delusions migrate freely from your dreams into waking consciousness. Eventually your limbs, bowel and bladder escape your control. You drift into a silent stupor, and after a year or two of bedsores and diaper rash, you stop swallowing food. Death, when it comes, is a formality.

When the German psychiatrist Alois Alzheimer first described this awful disease in 1906, it was mercifully rare. Most people died young enough to avoid it. But life expectancy has risen dramatically since then (from 47 years to 77 years in the United States), and the burden of Alzheimer's has grown accordingly. Some 4 million Americans--one in five of those 75 to 84 and nearly half of those 85 and older--are now afflicted. And if that sounds dire, consider what's in store for our increasingly aged society. By one estimate, the number of U.S. Alzheimer's sufferers will approach 6 million by the end of this decade and could hit 14 million by midcentury.

Countless baby boomers are now confronting the needs of stricken parents, and realizing that their best efforts to stay healthy only raise the odds that they'll survive to meet the same fate. Unlike heart disease, which has well-known risk factors, Alzheimer's is still hard to predict. And today's treatments provide only modest symptomatic relief, if that. But the story is rapidly changing. "We've learned more about Alzheimer's in the past 15 years than in the previous 85," says Dr. Bruce Yankner of Harvard Medical School. In the past year alone, scientists have made several critical discoveries about how Alzheimer's destroys the brain, and their findings have raised tantalizing possibilities for treatment. Drugmakers are now pursuing a half-dozen new remedies, and predicting that one or more will reach the market within seven years. "We've never been at a stage like this," says Dr. Marcelle Morrison-Bogorad of the National Institute on Aging, "where we have so many leads to follow."

For all the recent progress, there is still no foolproof way to diagnose Alzheimer's in a living person. With a patient showing signs of dementia, the physician's main task is to rule out other possible causes, such as strokes, tumors or vitamin deficiencies. When 80-year-old retired architect Morley Madden complained several years ago that he could no longer finish the household projects he started, his family doctor doubted anything was seriously wrong. But when Madden scored badly on a simple cognitive test called the Mini Mental State Exam and an MRI scan showed no signs of a stroke, Alzheimer's became the best name for his problem.

What was actually happening to his mind? At least two things. As Alzheimer discovered from autopsy studies, victims' brains are littered with wads of sticky debris, or plaques, and their neurons contain twisted protein filaments known as tangles. Until recently, scientists could only guess about the significance of these lesions. "No one even knew what they were made of," says Paul Greengard, director of Rockefeller University's Fisher Alzheimer Center. "Now we know what they're made of, and we're beginning to understand what causes their formation."

The first real clue to the mystery came in the late 1980s, when scientists identified a molecule called APP, or amyloid precursor protein. …