Research highlight

Neuroscience: Structure of Alzheimer’s amyloid beta fibrils revealed

Nature Communications

October 30, 2019

The structure of amyloid beta (Aβ) fibrils isolated from the brain tissue of patients with Alzheimer’s disease and cerebral amyloid angiopathy is published in Nature Communications this week. These findings provide new insights into the structural basis of the disease and may aid drug development.

Alzheimer’s disease is a progressive neurodegenerative disease and one of its hallmarks is the deposition of Aβ amyloid fibrils in plaques and vessel walls. Although Aβ amyloid fibrils generated in the laboratory are structurally well characterized, the structure of these fibrils in the brain has remained poorly understood.

Marcus Fandrich and colleagues purified Aβ amyloid fibrils from the brain tissue of three patients with Alzheimer’s disease after their death and used cryo-electron microscopy to analyse their structure. The authors identify three distinct but structurally related Aβ fibril morphologies in all three patient samples and determined the molecular structure for one of them. Unexpectedly, the structure of the brain-derived fibrils differs substantially from that of Aβ amyloid fibrils prepared in the laboratory. For example, the brain-derived Aβ amyloid fibrils were right-hand twisted and their peptide fold was distinctly different to previously analysed fibrils.

This structure highlights the importance of characterizing patient-derived amyloid fibrils. Furthermore, it provides insights into the effects of Alzheimer’s disease-causing mutations in Aβ and could potentially aid the development of drugs that may prevent the formation of these fibrils.

doi: 10.1038/s41467-019-12683-8

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