10 January 2019 - Research

Alzheimer's-affected brains are riddled with so-called amyloid plaques: protein aggregates consisting mainly of amyloid-β. However, this amyloid-β is a fragment produced from a precursor protein whose normal function has remained enigmatic for decades. A team of scientists from the de Wit and De Strooper lab at the VIB-KU Leuven Center for Brain & Disease Research, teamed up with the Farrow lab and collaborators in Israel and the US, to uncover that the amyloid precursor protein modulates neuronal signal transmission through binding to a specific receptor.

More than 30 years have passed since the amyloid precursor protein was first identified. In the late 1980s, several research teams across the globe traced the protein fragment found in amyloid plaques back to a gene located on chromosome 21. The gene encodes a longer protein that is cleaved into several fragments, one of which ends up in amyloid plaques.

Decades of research have focused on the cleavage process that leads to the formation of the amyloid-β fragment and its subsequent aggregation, in the hope of identifying new therapeutic avenues for Alzheimer's. Meanwhile, an important question remained unanswered: what does the rest of the amyloid precursor protein actually do?

In search of a binding partner

To answer this question, Heather Rice, a postdoctoral researcher at the VIB-KU Leuven Center for Brain & Disease Research, set out to identify the nerve cell receptor that interacts with the amyloid precursor protein. The researchers identified a receptor present at the synapse, the structure where two different neurons connect to pass on signals.

A collaborative effort

Rice could also frequently be found at NERF, where she worked closely with Daniel de Malmazet from the Farrow lab. We got together with Daniel to find out more about the collaborative journey that led to these important findings.

Daniel, how did the collaboration with you at NERF help move this project along?

"I helped Heather to validate her exciting findings in vivo. We set up a surgery to expose the mouse hippocampus (CA1) and visualize basal activity of the CA1 neurons using a calcium indicator. We then tested with Heather how this activity is affected when soluble APP peptide is applied."

Demalmazet Daniel

What was it like for you to collaborate on this project with colleagues at the VIB-KU Leuven Center for Brain & Disease Research?

"I think the most exciting part was seeing such a wide spectrum of science in one project. I realized how nicely our computational and engineering skills could complement an intricate biochemical study and got inspired to collaborate more."

"Working with Heather was both exciting and inspiring. I was impressed by how we approach problems from different angles, given our different scientific backgrounds, which in the end helped us succeed together."

The results were published today in Science.

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