Specific Imbalance Between Two Peptides may Cause Alzheimer's

Researchers at Rensselaer Polytechnic Institute have challenged the current theory on the causes and prevention of Alzheimer’s disease, suggesting that a specific imbalance between two peptides may be responsible for preventing this form of dementia.

"We have found that two peptides, AB42 and AB40, must be in balance for normal function," said Chunyu Wang, lead researcher and assistant professor of biology at Rensselaer.

"They are like the Yin and Yang in Taiji, an ancient Chinese philosophy. When the peptides are produced in the correct proportions, the brain is healthy; but when that delicate balance is changed, pathological changes will occur in the brain and the person’s memories become hazy, leading to eventual dementia," the researcher added.

If Wang’s hypothesis turns out to be correct, the addition of AB40 may help stop the disease’s development.

He, however, admits that further research is required to prove his hypothesis.

The two peptides identified by Wang have been previously found in deposits, called senile plaques or amyloid plaques, in brains afflicted with Alzheimer’s disease. These plaques, mainly composed of AB42 fibrils, are a hallmark of Alzheimer’s disease.

During the study, Wang used the advanced Nuclear Magnetic Resonance (NMR) machines to monitor the formation of harmful AB42 fibrils in the presence of different levels of AB40. He found that as AB40 levels increased, the aggregation of AB42 fibrils sharply decreased, protecting benign AB42 monomers.

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"We have found that the ratio of AB40 to AB42 plays a key role in AB42 aggregation," he said.

"The current mode of thinking in Alzheimer’s emphasises the toxic role of AB42 but neglects the protective role of AB40. Combined with previous work on AB40 by many other groups, our data suggest that AB40 has an equally important, protective role in Alzheimer’s. Thus AB42, the bad molecule, and AB40, the good molecule, are like Yin and Yang in Taiji. The brain can only function normally when they are in balance," he added.

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The study, to be published in the Journal of Molecular Biology, shows that when there is 15 times more AB40 than AB42, the formation of AB42 fibrils is almost completely stopped.

"This means that the introduction of AB40 to tip the peptide balance toward AB40 could potentially halt or slow down the progression of the Alzheimer’s in the human brain," Wang said.

Wang plans to continue investigating how AB40 halts the formation of AB42 fibrils.

"This has the potential to become a simple therapy to prevent the formation of toxic AB42 species. I plan to continue my research on the role of AB40 and hope that we can test this theory on human neurons, animal models, and someday in clinical trials. One critical advantage of using AB40 for the prevention or therapy for Alzheimer’s is that AB40 is already known to be largely free of side effects at near physiological concentration," he said.

Source: ANI
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