Scientists capture images of Alzheimer’s plaque precursor

Using a nuclear magnetic resonance technique, University of Illinois at Chicago (UIC) chemists have obtained the first molecular-level images of precursors of bundled fibrils that form the brain plaques seen in Alzheimer’s disease.

Microscopic bundled fibrils made of proteins called amyloid-beta are presumed to be the toxic culprits in the senile plaques found in the brain with Alzheimer’s. But there is increasing evidence that even smaller assemblies of amyloid-beta found prior to formation of pre-fibrils are the real nerve-killers.

By using a high-resolution solid-state nuclear magnetic resonance, or SSNMR, the UIC researchers have now determined this structure. The technique uses what is called time-resolution SSNMR to view nanoscale spectral images of this chemical formation. Thioflavin, a dye commonly used to stain amyloid senile plaques, is applied to detect formation of the intermediate assemblies in florescence. The intermediate sample is then frozen to capture quickly changing spectral images of the molecules before they can self-assemble into fibril-forming sheets.

The resulting SSNMR ‘snapshots’ provide a structural diagram for finding molecular binding targets that may stop proteins from misfolding, which may stop Alzheimer’s disease from developing.

Yoshitaka Ishii, assistant professor of chemistry at UIC said the SSNMR technique may be used to study small chemical subunits involved in diseases such as Parkinson’s and prion diseases like mad cow or Creutzfeld-Jacob, to name just some of the 20 or so neurodegenerative diseases characterized by misfolding proteins.