Neurodegeneration: Taming tangled tau

Abstract

The protein Tau forms abnormal filamentous aggregates described as tangles in the brains of people who have dementia. Structures of two such filaments offer pathways to a deeper understanding of the cause of Alzheimer’s disease. See Article p.185

Figure 1 |. Structures of Tau protein filaments.

Fitzpatrick et al. extracted and imaged two types of abnormal Tau aggregate — straight filaments and paired helical filaments — from the brain of a patient who had Alzheimer’s disease. In both cases, individual Tau proteins form C shapes (the protein’s main chain is indicated by cartoon ribbons, the side chains are shown in grey), which stack together to form protofilaments. Here, 14 protein layers are shown in each protofilament. Both types of filament are composed of two identical protofilaments, connected at different interfaces. Notable features of the protofilaments include a steric zipper (a common structural motif in aggregated proteins, which repels water) and a β-helix region in which charged residues face outside and apolar residues face inside.