Alzheimer’s protein solved

Using X-ray crystallography, Yale scientists have discerned, for the first time, the atomic structure of a protein that is linked to Alzheimer’s disease.

Ya Ha, Ph.D., assistant professor of pharmacology, reported in August in Molecular Cell that he had observed an unusual feature of human amyloid precursor protein (APP). Rare mutations of APP cause Alzheimer’s at an early age in a small number of people. Researchers have been trying to determine what app does and how it converts to a smaller protein, amyloid beta-peptide, which forms neuronal and vascular amyloid deposits typical of Alzheimer’s disease.

Ha and Yongcheng Wang, Ph.D., a postdoc in his laboratory, found that APP consists of two long rodlike molecules that form a tight complex, with the head of one molecule touching the tail of the other.

“That observation suggested a novel possibility,” said Ha, “that app may function to mediate cell-to-cell contact by interacting with itself.”