Researchers have untangled some of the neurological events that may ultimately lead to Alzheimer's disease. Two new studies show that a protein implicated in this form of dementia can infect other neurons to spread disease across the brain. These problematic proteins clump together, which can lead to cognitive problems.

A protein's shape—the way its chains of amino acids fold—determines its function. If a protein misfolds, its structure and function change. In Alzheimer's, researchers have long suspected that misfolded versions of a protein called amyloid-beta might travel from cell to cell and cause more amyloid-beta proteins to take on a deformed shape.

To test this idea, biophysicist Jan Stöhr of the University of California, San Francisco, and his colleagues injected synthetic amyloid-beta proteins into the brains of mice and found that plaques began to form in less than six months. Even when the synthetic proteins were injected into only one side of the brain, over time plaques materialized throughout the organ, the researchers found. “If these aggregates are not cleared by the brain, they will start to recruit more amyloid-beta peptides into the diseased conformation, and the spread throughout the brain begins,” Stöhr says. The results appeared in the June Proceedings of the National Academy of Sciences USA.

In a separate study using a cell culture, a team of researchers led by Martin Hallbeck of Linköping University in Sweden tracked amyloid-beta transmission from neuron to neuron for the first time. The results, published in the June 27 Journal of Neuroscience, also show that neurons containing misfolded amyloid-beta can cause neighboring, connected neurons to break down, eventually infecting the entire culture.

The current task for scientists is to figure out what other proteins and cellular machinery assist the infection process. Targeting these helpers may be an effective option for developing Alzheimer's therapies, Stöhr says.

This article was originally published with the title Planting Seeds of Dementia.

6 Comments

1. 1. alan6302 08:05 AM 11/22/12

   The first step in brain damage is seeing a doctor.

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2. 2. lowndesw in reply to alan6302 09:10 AM 11/22/12

   alan6302, are you saying that to avoid brain damage, don't "see a doctor"??

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3. 3. igorm 09:52 AM 11/22/12

   If this is indeed the mechanism of the disease, it would be quite similar to the human "Mad cow" disease mechanism, where a malformed prion protein is to blame. Apparently, these malformed prions cause more prions to turn into the malformed shape.
   
   Very strange is the fact that in both these diseases the brain is the affected organ. Are there other diseases caused by "multiplying" malformed proteins in other organs?

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4. 4. jtdwyer 11:03 AM 11/22/12

   What's not explained in this brief article is how proteins can become misfolded and haw the presence of some misfolded proteins can cause others to be misfolded...
   
   It would seem that perhaps the mechanism for producing the proteins (DNA transcription?) must be somehow damaged, and possibly the misfolded proteins might also introduce damage to the production mechanism.

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5. 5. AllanRBrewer in reply to jtdwyer 03:16 PM 11/22/12

   In these cases, the DNA is transcribed correctly. All proteins dynamically fold towards an energy minimum (usually the correct shape) and unfold to some extent. In the case of prions, and apparently amyloid-beta, there is a "mis-fold" energy minimum as well as the correct fold energy minimum. Normally the mis-fold minimum shape is not attained because it is not on normal dynamic pathways, but the presence of a first mis-folded molecule happens to catalyse other molecules toward the mis-fold energy minimum.

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6. 6. jtdwyer in reply to AllanRBrewer 03:27 PM 11/22/12

   Thanks for explaining. Not to be a pest, but I have to wonder why the presence of both correctly and incorrectly folded molecules would apparently preferentially produce misfolded molecules - are they perhaps the lower energy configuration of the two?

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