In Alzheimer’s disease, the atrophy of the nerve cells in the brain leads to memory problems and cognitive impairments. Initially, the neurons cell’s junctions called synapses are destroyed, but over time, the whole cell dies. In the brain of a person with severe Alzheimer’s one can find plaques mainly enriched of fibrillar aggregates of proteins’ amyloid beta and tau.

The scientific community has not been able yet to determine the exact composition of the amyloid plaques nor the high-resolution structure of the fibrils made by amyloid beta 42.

The 50 million people currently suffering from dementia need more effective treatments. I believe our study will significantly contribute to the puzzling fight against Alzheimer’s disease.

It is known that the protein’s aggregates found in Alzheimer’s brains, known as fibrils, consist of twisted threads. But in a new study published in the Proceedings of the National Academy of Sciences, PNAS, a team of researchers from Lund University reveals that each fibril is made up of two threads, known as filaments and four peptides’ copies per plane.

“A deeper understanding of amyloid beta 42 fibril structure could guide the development of drugs that inhibit the formation and spreading of harmful oligomers”, says Veronica Lattanzi, a biochemistry doctoral student at NanoLund, Lund University.

Using X-rays and neutron scattering

To study amyloid beta 42 in detail, the research team carried out advanced X-ray and neutron scattering experiments at the Chemistry Centre in Lund and at the Paul Scherrer Institute in Switzerland. Thanks to the scattering pattern created in the lab, the researchers were able to identify a number of previously unknown features of the fibril.

“In addition, by combining small angle scattering studies with solid-state NMR established we were able to localize the amino acids residues on the fibril surface itself,” says Veronica Lattanzi.

Alzheimer’s is a fast-growing disease that causes great suffering for the affected individuals as well as their families. This summer, the US Food and Drug Administration approved the first symptom-relieving drug. Aducanumab is an antibody that redirects beta-amyloid, limiting the formation of toxic oligomers.

“The 50 million or so people currently suffering from dementia need more effective treatments. I believe our study will significantly contribute to the puzzling fight against Alzheimer’s disease”, says Veronica Lattanzi.

The study is published in the scientific journal Proceedings of the National Academy of Sciences, PNAS: Amyloid β 42 fibril structure based on small-angle scattering