A team of American chemists, including a UT professor, recently discovered that differences in brain protein structures can contribute to the development of Alzheimer’s disease.

Alzheimer’s is a neurodegenerative disease that causes memory loss and eventually death. It is associated with the buildup of deformed proteins called beta amyloid plaques in the brain. 

There is currently no treatment that slows the disease, which spurred a team of researchers to investigate the mechanisms behind Alzheimer’s. Their findings were published in Proceedings of the National Academy of Sciences of the United States of America on Aug. 24. 

Amyloid precursor proteins, which scientists think are involved in synapse formation and waste management, are threaded through membranes in the brain. Normally, enzymes will snip off parts of these proteins into fragments called amyloid beta proteins. The snipped fragments are typically degraded within the neuron as waste products.

In some people, the amyloid beta fragments remain and build up, forming clumps or plaques within the brain. These plaques are associated with symptoms such as late-age onset dementia. Dave Thirumalai, co-author of the study and chair of UT’s chemistry department, said the research team found that protein structure interacts with membrane thickness and composition in a way that can create plaques.

“We realized that we needed to go to the beginning,” Thirumalai said. “We wanted to know what [amyloid beta] looks like before it’s cut and what are the consequences of the cleaving process itself.”

The proteins differ between people, and the amyloid beta fragments aren’t always the same size, Thirumalai said, making it difficult to produce pharmaceuticals that target these unique molecules.

“Suppose that you have software code that does speech recognition and that code was not so specific,” Thirumalai said. “You say, ‘Please call my mother’, and instead it reads it as ‘Call your ex-boyfriend.’ You don’t want that — in life, you want important things to be more specific.” 

John Straub, chemistry professor at Boston University and co-author of the paper, said the team hopes their results will provide insight into the structural basis behind Alzheimer’s drugs, but the development of these drugs could be a long way away.

“Our findings are important, but there is no immediate connection to treatments,” Straub said. 

Thirumalai said that although they haven’t yet succeeded, drug companies are becoming more interested in preventing the reactions that cause Alzheimer’s.

Current Alzheimer’s treatments are designed to manage symptoms until end of life, because the disease currently has no cure. According to a report by the Food and Drug Administration, while there are many promising drug developments, none of their clinical trials have shown any improvement in patients.

Thirumalai said that the team will continue to look into the mechanisms behind Alzheimer’s, such as how cholesterol and seemingly benign mutations can affect amyloid beta precursor proteins.

“Initially we were worried about what happens to products after cleavage, but we realized that we need to go to the beginning,” Thirumalai said. “Our study is just the start of something.”