Porous nanodevices cage up suspected precursors of Alzheimer’s disease

There are many unknowns around the causes of Alzheimer’s, but one of the leading suspects is amyloid beta plaques. These form from amyloid peptides, and while some see these biomarkers as a chance to detect the disease in its early stages, others see them as an opportunity to intervene and possibly stop it altogether. A newly developed nanodevice could give these efforts a potent shot in the arm, by capturing these peptides and clearing them away before they aggregate into harmful plaques.

The role that amyloid beta plaques play in Alzheimer’s is still a matter of scientific debate. While failed clinical trials testing out anti-amyloid drugs have given many researchers in the field pause, large-scale studies continue to implicate these toxic clumps in the cognitive decline associated with the disease.

For example, the first data from one long-running US government trial last month demonstrated that elevated levels of amyloid proteins can act as an effective presymptomatic sign of Alzheimer’s. But it is a byproduct of these proteins that the researchers behind the new study have squarely in their sights.

“The β-amyloid peptides arise from the breakdown of an amyloid precursor protein, a normal component of brain cells,” says Rosemarie Wilton, a molecular biologist at Argonne National Laboratory and leader of the research team. ​“In a healthy brain, these discarded peptides are eliminated.”

If left to their own devices, these peptides can go onto to assemble into the amyloid beta plaques, which are thought to go on to affect neural connectivity and the wellbeing of brain cells. Wilton and her team have been investigating ways to gather up these peptides soon after they break away from the proteins, and have created an innovative nanodevice that has shown real promise in early testing.

The device is made from silica and consists of a porous, spherical structure that is coated in antibody fragments that recognize and strongly bind to the target peptides with high selectivity. These were first investigated through in vitro experiments where the nanodevices were tested alongside versions without the antibody fragments. They were for to sequester the peptides and prevented their aggregation with more than 90 percent more effectiveness than the control devices.

In vivo experiments followed, where the nanodevices were shown to be non-toxic to living cells. They were then tested in mice with Alzheimer’s, where they led to a 30-percent suppression in plaque formation, compared to the control group.

“We’ve taken building blocks from nanotechnology and biology to engineer a high-capacity ‘cage’ that traps the peptides and clears them from the brain,” says Argonne National Laboratory’s Elena Rozhkova.

The researchers have high hopes for their new nanodevices, flagging the possibility of loading them up with different antibodies that target molecules implicated in other neurodegenerative diseases, including Huntington’s disease and Parkinson’s disease, which also involve the abnormal aggregation of proteins.

The research was published in the journal Advanced Functional Materials.

Source: Argonne National Laboratory

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