Rensselaer Polytechnic Institute researcher Chunyu Wang and his team follow the trail of two genetic mutations a€" V44M and V44A a€" known to cause FAD, and show how the mutations lead to biochemical changes long linked to the disease.
The hallmark of FAD is the accumulation of the Amyloid Beta 42 peptide (a short chain of amino acids) in unusually high concentrations within the brain.
In a healthy brain, Amyloid Beta-42 and a similar peptide, Amyloid Beta-40, are found in a ratio of about 1 to 9.
In a brain affected by FAD, this ratio is much higher. The two peptides are nearly identical: Amyloid Beta 40 is a chain of 40 amino acids in length; Amyloid Beta 42 is 42 amino acids in length. However, Amyloid Beta 42 is much more toxic to neurons and plays a critical role in memory failure.
"The mutations that cause FAD lead to an increased ratio of Amyloid Beta 42 over Amyloid Beta 40," Wang, an associate professor of biological sciences within the School of Science, director of the biochemistry and biophysics graduate program, and member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies, said.
"That's the biochemistry, and that has been observed by many people," Wand said.
Wang's team used solution nuclear magnetic resonance spectroscopy to study the three-dimensional structure and dynamics of the transmembrane portion of APP affected by the two genetic mutations, and they discovered that the mutations cause a critical change to the T48 amino acid.
The study is published in the journal Nature Communications.
--ANI (Posted on 11-01-2014)