( ned its attention to figuring out ways ...)A new century of Alzheimer's disease research,Health

ned its attention to figuring out ways to disrupt AB production. Some researchers, such as Dr. Younkin, believed that in the brains of people who have Alzheimer’s, AB42 is deposited first, providing the initial toxic damage that leads to plaque formation, and then to disruption of tau inside neurons. The concept is known as the amyloid cascade hypothesis and is now accepted by many Alzheimer’s researchers almost as a gospel truth.

Early laboratory analysis of AB42 showed that the extra two molecules seemed to form a hook on the amyloid protein, making it more likely to stick to other amyloid proteins in the brain. Thus, researchers concluded that AB42 is highly prone to forming deposits. Synthesized particles of AB42 will fuse to each other within hours in an animal’s brain, but weeks are required for AB40 to adhere. More recent research has shown that the AB42 protein folds in such a way that it creates a pleated-sheet-like “template” that acts to chemically attract other proteins, and together these proteins grow in a crystalline fashion like a snowball emerging from a single icy flake.

“With a potential target, many in the pharmaceutical industry who want to design treatments for AD began bearing down on the issue, and that effort has completely turned around the prospects of finding something that could eventually help our patients,” Dr. Younkin says.

Now more than 100 mutations have been found in the three genes that cause early Alzheimer’s, and all increase production of AB42.

Of the AB produced normally in humans, 5 percent to 20 percent is AB42. As people grow older, small numbers of plaques and tangles form. The risk that these lesions will cause dementia increases with age; half of all people 85 and older are believed to have some stage of Alzheimer’s. Researchers think this common form of Alzheimer’s is triggered by a combination of normal genetic susceptibilities and other damage, such as from head trauma or unknown env
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