Neuroscience: Zooming in on protein aggregates related to Alzheimer’s disease

A close-up view of so-called tau filaments found in the brain of a patient with Alzheimer’s disease is published online in Nature this week. Filaments form by aberrant aggregation of Tau protein, and different conformations of these tau filaments are a hallmark of various neurodegenerative diseases. The newly determined molecular structures may help to improve our understanding of the role of these protein assemblies in Alzheimer’s disease.

Abnormal aggregates of tau filaments in the brain are associated with neurodegeneration and dementia; these filaments may hold clues to how neurodegenerative diseases develop and are important targets for treatments. However, a lack of high-resolution molecular structures has hampered our understanding of their role in neurodegeneration. Addressing this issue, Sjors Scheres, Michel Goedert and colleagues present the first cryo-electron microscopy structure of tau filaments from the brain of a 74-year-old woman with a confirmed diagnosis of Alzheimer’s disease. They provide a detailed description of the distinct helical and straight filaments, which may help to explain why these filaments form aggregates in the brain.

The structures are determined using an imaging technique called cryo-electron microscopy, which studies samples at very low temperatures and allows atomic characterization of amyloid filaments from patient-derived material. The authors suggest that this technique opens up new possibilities for studying the molecular mechanisms that underlie a wide range of neurodegenerative diseases.