Diagnosis for Alzheimer’s Tested

Scientists hope to detect fatal disease in early stages

WASHINGTON, Sept. 23 — Alzheimer’s disease, which can be confirmed only after death, could be diagnosed in its early stages if a new test works as well in humans as animals. Researchers hope early diagnoses could lead to treatments that would delay the fatal disease. The ability to diagnose the disease in its early stages would be important because it would allow any new therapy to be started before much damage had been done, said Dr. William E. Klunk, a member of Bacskai’s group, who is leading the human study at the University of Pittsburgh School of Medicine.

SCIENTISTS WERE able to diagnose the disease in mice using a chemical called PIB, which was able to cross the blood-brain barrier and bind to the amyloid plaques in the animals’ brains. The plaques, believed to be a cause of Alzheimer’s, were identified by detecting the PIB. The chemical quickly cleared out of the brains of mice without the disease, according to a team of researchers led by Dr. Brian J. Bacskai at Massachusetts General Hospital. The next step, already under way in Pittsburgh and in Uppsala, Sweden, is to test the chemical in people.

Currently, Alzheimer’s sometimes is indicated by symptoms, but a definite diagnosis can be made only after death by inspecting the victim’s brain. While medicine has no current therapy for Alzheimer’s, approaches from drugs to a vaccine are being studied.  

The ability to diagnose the disease in its early stages would be important because it would allow any new therapy to be started before much damage had been done, said Dr. William E. Klunk, a member of Bacskai’s group, who is leading the human study at the University of Pittsburgh School of Medicine. Their findings are being published in this week’s online issue of Proceedings of the National Academy of Sciences. “All the evidence points to the fact that (Alzheimer’s) pathology starts a decade or more before symptoms appear,” said Klunk, so having a good way to detect plaques could get treatment started early.

The mouse studies confirmed that PIB binds directly to the amyloid plaques associated with Alzheimer’s. Researchers studied the tissue through a hole in the skulls of the mice, using a multiphoton microscope that shows such minute tissues.  

PET scans used on humans lack such fine resolution, but Klunk said they can detect the presence of PIB in areas of the brain, and knowing that the chemical binds to the plaques would inform doctors that the problem was developing.“It’s like looking down from 30,000 feet and seeing a forest, but you can’t tell what kind of trees are there,” he said. Bacskai’s “technique takes us to ground level.”

Bacskai said PIB has been found to have no side effects. When injected in the tails of mice it moved quickly to the brain and bound to the plaques, remaining detectable for up to three days in some cases. When the mouse brains were dissected later, researchers were able to determine that PIB — Pittsburgh compound B — does not bind to white matter in the brain.

The finding was welcomed by Dr. F. Reed Murtagh, director of neuroradiology at the University of South Florida, who has also studied ways of detecting Alzheimer’s. Murtagh, who was not part of Bacskai’s team, called the development terrific because it could lead to diagnosis in people. “Nobody can diagnose definite AD — yet. This new stuff might allow us to do that,” he said.

What is Alzheimer's disease?How common is it?What causes it?How is it diagnosed?Can it be treated?What are the warning signs?
Alzheimer's is a degenerative brain disease that usually begins gradually, causing a person to forget recent events or familiar tasks. How rapidly it advances varies from person to person, but the disease eventually leads to confusion, personality and behavior changes and impaired judgment. Communication becomes more difficult as the disease progresses, leaving those affected struggling to find words, finish thoughts or follow directions. Eventually, most people with Alzheimer’s disease become unable to care for themselves.

One in 10 people over 65 and nearly half of those over 85 suffer from Alzheimer’s disease. Today, 4 million Americans have the condition. That number could jump to 14 million by the year 2050 unless prevention methods are developed.

Scientists still are not certain of the disease's cause. Advancing age and family history are risk factors. Researchers are exploring the role of genetics in the disease, but most agree it's caused by a variety of factors.  There is no single, comprehensive diagnostic test for Alzheimer’s disease. Instead, doctors rule out other conditions through a process of elimination. They usually conduct physical, psychological and neurological exams and take a thorough medical history. Diagnosis is about 90 percent accurate, but the only way to confirm it is through autopsy.

There is no medical treatment currently available to cure or stop the progression of Alzheimer's disease. There are currently four FDA-approved Alzheimer's drugs — Cognex, Aricept, Exelon and Reminyl — that may temporarily relieve some symptoms of the disease. Several other drugs are in development.

Common symptoms of Alzheimer's disease include:

  • Memory loss that affects job skills
  • Difficulty performing familiar tasks
  • Problems with language
  • Disorientation to time and place
  • Poor or decreased judgment
  • Problems with abstract thinking
  • Placing items in inappropriate places
  • Rapid changes in mood or behavior
  • Dramatic changes in personality
  • Loss of initiative

© 2003 Associated Press.

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