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Subject:  Alzheimer's: amyloid, tau or both? Date:  11/13/2012  2:19 PM
Author:  WendyBG Number:  412905 of 479851

Wall Street Journal, November 9, 2012, 10:36 p.m. ET

An Outcast Among Peers Gains Traction on Alzheimer's Disease


..A protein called tau—which forms twisted fibers known as tangles inside the brain cells of Alzheimer's patients— may be largely responsible for driving the disease. ...

Although interest in tau is building, opinions about the cause of Alzheimer's remain deeply divided. Some scientists believe an interaction between beta amyloid and tau plays a central role. Others think there are many possible triggers, including some beyond beta amyloid or tau. ...

The disease was first identified in 1906 by German physician Alois Alzheimer, who studied the brain of a deceased woman who had suffered from dementia and documented the [amyloid] plaques and [tau] tangles that riddled the tissue. ...

Like all of the body's proteins, tau has a normal, helpful function—working inside neurons to help stabilize the fibers that connect nerve cells. But when it misfires, tau can clump together to form harmful tangles that kill brain cells. ...

In the early 1990s, Dr. Wischik and his colleagues compared the postmortem brains of Alzheimer's sufferers against those of people who had died without dementia, to see how their levels of amyloid and tau differed. They found that both healthy brains and Alzheimer's brains could be filled with amyloid plaque, but only Alzheimer's brains contained aggregated tau. What's more, as the levels of aggregated tau in a brain increased, so did the severity of dementia....
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The rest of the article is about the scientific controversy and about drug development.

Both amyloid and tau are proteins that are normally soluble in the cell's liquid internal environment. However, they change their configuration to become insoluble. Then they clump.

Alzheimer's disease resembles prion diseases in that the symptoms are caused by a buildup of misfolded, insoluble proteins.

The root cause of many diseases that are caused by misfolded proteins may be a defective proteasome, the complex mechanism for removing defective (including misfolded) proteins.

The main function of the proteasome is to degrade unneeded or d