UK MRC researchers reveal structures of tau filaments from Alzheimer's disease


Scientists at Britain’s Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) have uncovered the atomic structure of tau protein filaments, which lead to Alzheimer's disease.

The researchers used a technique known as cryo-electron microscopy (cryo-EM) to map in sufficient detail the tau filaments that were extracted from the brain of a patient who had died with Alzheimer's.

In addition, a new software developed by senior author Sjors Scheres and colleagues was used to calculate the structure of the filaments and to deduce the atomic arrangement inside them.

Sjors Scheres said: “It’s very exciting that we were able to use this new technique to visualise filaments from a diseased brain as previous work depended on artificial samples assembled in the laboratory.

“Amyloid structures can form in many different ways, so it has been unclear how close these lab versions resembled those in human disease.

“Knowing which parts of tau are important for filament formation is relevant for the development of drugs.

"Knowing which parts of tau are important for filament formation is relevant for the development of drugs."

“For example, many pharmaceutical companies are currently using different parts of tau in tests to measure the effect of different drugs on filament formation; this new knowledge should significantly increase the accuracy of such tests."

Tau is one of two types of abnormal ‘amyloid’ forms of protein that produce lesions in the brain, leading to Alzheimer's disease.

It forms filaments inside nerve cells and is believed to be associated with the loss of cognitive ability lesions in patients with the most common neurodegenerative disease.

The other protein amyloid-beta forms filaments outside nerve cells.

In future, researchers hope to uncover how tau protein may form different filaments in other neurodegenerative diseases.

The research was funded by the MRC, the European Union, US National Institutes of Health, the Department of Pathology and Laboratory Medicine, and the Indiana University School of Medicine.