Researchers have, for the first time, revealed the atomic structures of one of the two types of the abnormal filaments which lead to Alzheimer’s disease. Understanding the structures of these filaments will be key in developing drugs to prevent their formation.
The researchers, whose study is published today in Nature, believe the structures they have uncovered could also suggest how tau protein may form different filaments in other neurodegenerative diseases.
Alzheimer’s, the most common neurodegenerative disease, is characterised by the existence of two types of abnormal ‘amyloid’ forms of protein which form lesions in the brain. Tau forms filaments inside nerve cells and amyloid-beta forms filaments outside cells. Tau lesions appear to have a stronger correlation to the loss of cognitive ability in patients with the disease.
Almost thirty years ago, scientists identified tau protein as an integral component of the lesions found in Alzheimer’s and a range of other neurodegenerative diseases. But, until now, scientists have been unable to identify the atomic structure of the filaments.
The researchers extracted tau filaments from the brain of a patient who had died with Alzheimer’s disease. The filaments were then imaged using cryo-electron microscopy (cryo-EM). The researchers developed new software in order to calculate the structure of the filaments in sufficient detail to deduce the arrangement of the atoms inside them.
The researchers say that their study could lead to the development of new approaches to the diagnosis and treatment of Alzheimer’s disease.
Paper: “Cryo-EM structures of tau filaments from Alzheimer’s disease”
Reprinted from materials provided by the MRC.