When German physician Alois Alzheimer first identified the disease that bears his name, he had observed severe memory loss and confusion in a woman far too young for the dementia associated with advanced age. After she died, these unusual symptoms led Alzheimer to examine her brain at autopsy; only then did he discover distinctive, diagnostic markers—microscopic clumps of sticky plaque and tangled nerve fibers.

 

Fast-forward a century, and a race is on to invert that sequence and enable diagnosis of Alzheimer’s long before the onset of symptoms. An even more heated contest is under way to introduce drugs that can delay the loss of independence, quality of life, and even identity that Alzheimer’s entails. At the heart of both challenges is something called “the amyloid hypothesis.”

 

This hypothesis rests on the idea that in people with Alzheimer’s disease, a protein fragment normally found throughout the body somehow goes awry. Amyloid-beta, also known as “A-beta,” normally circulates between cells. But in 1984, scientists Dr. George Glenner and Caine Wong isolated A-beta within some of the types of distinctive brain damage Alzheimer noted under his microscope. In the mid-1990s, other Alzheimer’s disease researchers pushed that discovery further. Working independently, Dr. Steven Younkin and Dr. Dennis Selkoe used genetic information derived from a small subset of Alzheimer’s disease patients to sharpen the focus on a specific type of A-beta composed of 42 amino acids—just two longer than the typical A-beta fragment. According to the amyloid hypothesis, rogue A-beta builds up in the brain and disrupts the normal functions of brain cells, leading to inflammation, plaques, and brain cell death.

 

The drugs furthest along in the race to develop a treatment for Alzheimer’s target A-beta or A-beta 42 in some way. Flurizan, steered by Utah-based Myriad Pharmaceuticals, seeks to lower A-beta 42 production by inducing the body to produce shorter strings of A-beta. The drug is well into Phase III trials involving about 1,600 patients.

 

Nipping at its heels is bapineuzumab, a monoclonal antibody driven by Ireland-based Elan Pharmaceuticals and New Jersey-based Wyeth. Bapineuzumab, which aims to bind A-beta and clear it from the brain, is currently in Phase II studies involving about 200 patients, and Elan-Wyeth plans to launch a Phase III trial before the end of the year. 

 

If these drugs succeed in demonstrating a safe, disease-modifying effect, their impact on the market will be enormous. Nitasha Manchanda, an analyst with Massachusetts-based healthcare research firm Decision Resources, estimates that sales of Alzheimer’s-related drugs would leap from about $1.7 billion in 2006 to more than $5.6 billion in the United States in 10 years. That estimate, however, came before the recent failure of one key drug in a clinical trial. Nevertheless, she estimates that bapineuzumab, currently considered the more effective and costly, could bring in about $3.6 billion alone.

 

The reason for such a sizable market is obvious. According to the Chicago-based Alzheimer’s Association, more than 5 million Americans now have the condition, By 2050, the group estimates, with population growth and increasing life expectancy putting more people at risk, that figure could reach 16 million.

 

Alzheimer’s attacks the more complex aspects of brain function first, often destroying memory or the ability to think through a problem logically. Eventually, typically over the course of about eight years, cumulative brain damage proves fatal. According to a U.S. Senate report, public spending on Alzheimer’s may top $110 billion a year in direct and indirect care costs, but even funding on that scale does not cover all of the estimated $170,000 in additional lifetime care costs an Alzheimer’s patient faces.

 

 And medicine today can offer little help. The handful of Alzheimer’s-related drugs currently on the market, such as Pfizer’s Aricept or Forest Laboratories’ Namenda , only ease a few symptoms, most notably memory loss. Since they don’t address the underlying disease process, the drugs only aid some patients for a few years at most.

 

“Eventually, people decline to the same point they would have anyway,” says Dr. Adam Boxer, an Alzheimer’s specialist who directs studies of new therapeutic agents at the University of California, San Francisco. “The drugs just delay the effect. They’re just helping the brain to function a bit better while these devastating changes are going on.”