New Study Sheds Light on Progression of Alzheimer's Disease

From the WebMD Archives

March 21, 2000 (Atlanta) -- Protein deposits typically found in the brains of Alzheimer's patients may begin forming before symptoms of the disease are present and increase as the disease progresses, according to a recent study published this week in TheJournal of the American Medical Association (JAMA).

The study paints a more complete picture of the progression of Alzheimer's disease, linking the severity of dementia with the amount of plaque found in the brain. Plaque is made up of deposits of protein called beta-amyloid.

The study also established that, at least in one part of the brain, the beta-amyloid proteins found in the plaque occur before another Alzheimer's trademark, called neurofibrillary tangles, forms. These are tangles made of another protein called tau, and they are found inside the brain's cells.

"I think it is a particularly well done study that correlates the density and presence of amyloid with the level of dementia in a fairly good size patient population," says Bill Thies, PhD, vice president of medical and scientific affairs at the Alzheimer's Association in Chicago. "So in terms of showing a sequential relationship -- that is, if you have more amyloid, you have more dementia -- this paper is quite good."

From the very first description of Alzheimer's, researchers recognized that beta-amyloid plaque and tau protein tangles were present in the brains of patients with the disease, according to Thies.

"There has been fairly steady debate as to which is the cause of Alzheimer's, does one cause the other, and which comes first," he says. "And if you are going to try to treat it, where would you like to attack [it]: either at the formation of the plaque or at the formation of the tangles?"

A better understanding of the sequence of events leading up to Alzheimer's could help researchers target therapies for the disease.

Researchers led by Jan Näslund, PhD, from the Laboratory of Molecular and Cellular Neuroscience at Rockefeller University in New York, conducted analyses on the brain tissue of 79 nursing home residents who died between 1986 and 1997. Patients were excluded if they had abnormal brain changes caused by something other than Alzheimer's.

Researchers measured the amount of two different kinds of beta-amyloid proteins in five regions of the brain and found that patients who hadn't had Alzheimer's had lower levels than those who did have Alzheimer's. The average levels of both proteins were generally higher in patients who had in life had more severe Alzheimer's.

When the researchers looked at the tau protein tangles in the front part of the brain, a part of the brain involved only late in the disease's progression, they found increases in both beta-amyloid proteins came before the formation of the tangles, and that these increases occur before many symptoms of Alzheimer's are apparent.

"There has always been a lot of uncertainty about which of the many changes are the earliest and the most relevant for causing Alzheimer's, and which occur after the fact," Allan Levey, MD, PhD, tells WebMD. "It is still not absolutely clear; this study doesn't settle it completely, but it just gives more reasons for thinking that amyloid is important." Levey is a professor of neurology and director of the Alzheimer's Disease Center at Emory University in Atlanta.

"[The study] does provide more reason to study early changes that occur in the brain in Alzheimer's disease, and I think it will prompt further study in the role of tangles vs. amyloid in other brain regions," says Levey. "Ultimately it may help in the development of treatments."

Vital Information:

  • The brains of Alzheimer's patients contain plaques made of beta-amyloid protein found outside the cells and contain tangles of a protein called tau found inside the cells.
  • There has been a debate among the scientific community about which protein causes Alzheimer's, if one causes the other, and which one develops first.
  • New research shows that the beta-amyloid protein plaques are formed first and develop even before symptoms of the disease are present.