Seeing Alzheimer's amyloids

Brandeis and Leibniz Institut researchers show what protein clump looks like

A-beta peptide fibril shown using electron microscopy. Click here for more information.

In an important step toward demystifying the role protein clumps play in the development of neurodegenerative disease, researchers have created a stunning three-dimensional picture of an Alzheimer’s peptide aggregate using electron microscopy. The study, in this week’s issue of the Proceedings of the National Academy of Sciences, reports that researchers from Brandeis University in Waltham, Mass., and the Leibniz Institut in Jena, Germany, have shown—for the first time—how A-beta peptide, found in the brains of Alzheimer’s patients, forms a spaghetti-like protein mass called an amyloid fibril.

“This study is a significant advance regarding our understanding of how these fibrils are built from the A-beta peptide (Alzheimer's peptide),” said co-author Nikolaus Grigorieff, a biophysicist at Brandeis University and an investigator with the Howard Hughes Medical Institute. “People have been guessing for decades what these fibrils look like, but now we have an actual 3D image.”

In healthy people A-beta peptide does not aggregate, but in Alzheimer’s patients it clumps first and then forms long fibrils, like tentacles, in a so-called cross-beta structure. Scientists disagree whether it is the clumps that kill neurons in the brain or the fibrils. Grigorieff wants to discover which part of the amyloid structure is toxic; that would be an important step in designing drugs to prevent or treat disease.