The ingredient of the plaque deposits that form in brains ofAlzheimer's victims can be made by a normal metabolicpathway, researchers reported today in Science.

Previous research, including findings reported last year byAthena Neurosciences Inc. (NASDAQ:ATHN) of South SanFrancisco, Calif., indicated that the large protein that containsbeta-amyloid, called APP, normally releases a portion thatcontains only part of beta-amyloid. Scientists were at a loss toexplain how beta-amyloid deposits could form. Now theevidence is that another processing pathway exists, which doesmake fragments of APP containing beta-amyloid.

It remains to be determined what would make this pathwaytake precedence over other routes of processing.

Researchers at the The Upjohn Co. of Kalamazoo, Mich., andcollaborators in Japan and at Case Western Reserve Universityin Cleveland isolated fragments from human brain that containthe beta-amyloid sequence of amino acids. The researchers saidthat proteins "essentially identical" to two fragments theyfound can aggregate and form deposits when overexpressed inlab-grown cells, and can also kill certain cells.

The Case Western group, working with amyloid expert DennisSelkoe at Harvard, then showed that the lysosome organelles incells can form the potentially damaging protein fragments.

Still unresolved is the chicken-and-egg question of what comesfirst, the disease or the deposits. Also, as the researchers noted,it is not yet known whether mutations identified in somefamilies with inherited Alzheimer's disease "alter endosomal-lysosomal processing in a way that is amyloidogenic."

-- Roberta Friedman, Ph.D. Special to BioWorld

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