LOS ANGELES, Apr 23 (Reuters) - The irreversible brain disorder Alzheimer's Disease may be caused by inflammatory processes associated with aging and not--as generally believed--by plaque-like deposits in the brain, researchers said on Friday.

The scientists from the University of Southern California in Los Angeles and Northwestern University in Evanston, Ill., said their findings could open new avenues of exploring ways to treat or even cure the disease.

Their findings, published this week in the journal "Trends in Neurosciences," still lays the blame for Alzheimer's on a molecule called amyloid beta, but traces the basic cause of the disease to the formation of toxic proteins rather than the build-up of plaque and tangles inside nerve cells in the brain.

Amyloid plaques are hard waxy deposits consisting of protein and polysaccharides that result from the degeneration of tissue.

Alzheimer's, which affects about four million Americans, starts with memory loss and progresses to profound dementia and death. There is no cure, although there are a few drugs that provide temporary relief for some symptoms of the disease.

"We were able to identify in laboratory test tubes a new kind of toxic activity that is implicated as a root cause of Alzheimer's," Dr. Caleb Finch, director of the Neurogerontology Division at the USC Andrus Center's Gerontology Research Institute, told Reuters in an interview.

The researchers discovered a novel form of wadded-up amyloid called "amyloid b-derived diffusible ligands"--ADDLs or "addles" for short--that form in the presence of certain inflammatory proteins in the brain. They have chemical and toxicological properties quite different from either single beta-amyloid molecules or clumps of the molecules called fibrils.

For nearly two decades, Alzheimer's research has focused on ways to prevent the formation of fibrils, which coalesce into even larger deposits in the brain known as plaques, which have been shown to kill nerve cells in the brain.

"ADDLs come before fibrils," Finch said.

ADDLs AFFECT BRAIN CELLS THAT ATROPHY

Also unlike fibrils, ADDLs are highly selective in their toxicity. The researchers found that ADDLs affect only the same types of brain cells that atrophy in Alzheimer's patients. Fibrils, however, kill a broad range of nerve cells--even destroying cell types that remain healthy right up until patients die.

ADDLs are also soluble, which means they are free to diffuse everywhere in the brain. Fibrils are confined to the specific locations where they first form and these locations correspond poorly with the brain areas that wither as Alzheimer's progresses, according to the researchers.

"These soluble forms may be the answer to the riddle as to why fibrils don't correlate with areas of that brain that are damaged by Alzheimer's," Finch said.

The researchers also suggest that ADDLs begin to interfere with the brain's basic mechanism of long-term memory well before they reach levels high enough to kill brain cells.

"ADDLs result from certain types of inflammatory proteins. If we can interfere with this process, we can affect the progress of the disease," Finch said.

Given this, the concept of developing an antibody-based vaccine to treat or even prevent Alzheimer's makes sense, the researcher said. "A couple of years ago, people thought the vaccination approach was the craziest idea. But if the real target is the soluble molecule and not the fibrils, it is a consistent approach," Finch said.

From ReutersHealth