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GEN News Highlights : May 30, 2007

Protein Imbalance May Cause Alzheimer’s

AB40 peptide prevents AB42 peptide from forming amyloid plaques.

A specific imbalance between two peptides, amyloid beta-peptide with 40 amino acids (AB40) and AB42, may be the cause of Alzheimer’s disease, according to researchers at Rensselaer Polytechnic Institute.

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

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

In the study, Dr. Wang used NMR 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.

Dr. Wang’s experiments show that when there is 15 times more AB40 than AB42, the formation of AB42 fibrils is almost completely stopped. The research will be published in the June edition of the Journal of Molecular Biology.