Scientists have developed synthetic peptides that target and inhibit build up of small, toxic proteins which trigger Alzheimer's disease.
The research, published in the Proceedings of the National Academy of Sciences, may be pave the way for treating the neurodegenerative disorder at an early stage.
Alzheimer's is a disease of aggregation. Neurons in the human brain make a protein called amyloid beta. Such proteins on their own, called monomers of amyloid beta, perform important tasks for neurons.
However, in the brains of people with Alzheimer's disease, amyloid beta monomers have abandoned their jobs and joined together.
First, they form oligomers -- small clumps of up to a dozen proteins -- then longer strands and finally large deposits called plaques.
For years, scientists believed that the plaques triggered the cognitive impairments characteristic of Alzheimer's disease. However, newer research implicates the smaller aggregates of amyloid beta as the toxic elements of this disease.
Researchers at the University of Washington in the US have developed synthetic peptides -- which are designed to fold into a structure known as an alpha sheet -- can block amyloid beta aggregation at the early and most toxic stage when oligomers form.
The team showed that the synthetic alpha sheet's blocking activity reduced amyloid beta-triggered toxicity in human neural cells grown in culture, and inhibited amyloid beta oligomers in two laboratory animal models for Alzheimer's.
These findings add evidence to the growing consensus that amyloid beta oligomers -- not plaques -- are the toxic agents behind Alzheimer's disease.
The results also indicate that synthetic alpha sheets could form the basis of therapeutics to clear toxic oligomers in people, according to Valerie Daggett, a professor at University of Washington.
"This is about targeting a specific structure of amyloid beta formed by the toxic oligomers," said Daggett.
"What we've shown here is that we can design and build synthetic alpha sheets with complementary structures to inhibit aggregation and toxicity of amyloid beta, while leaving the biologically active monomers intact," she said.
The peptides protected laboratory animals from toxic oligomer damage. In brain tissue samples from mice, the team observed an up to 82 per cent drop in amyloid beta oligomer levels after treatment with a synthetic alpha sheet peptide.
Administering a synthetic alpha sheet to living mice triggered a 40 per cent drop in amyloid beta oligomer levels after 24 hours.
In the common laboratory worm Caenorhabditis elegans, another model for Alzheimer's disease, treatment with synthetic alpha sheets delayed the onset of amyloid beta-induced paralysis.
Daggett's team is continuing experiments with synthetic alpha sheets to engineer compounds that are even better at clearing amyloid beta oligomers.
"What we're really after are potential therapeutics against amyloid beta and diagnostic measures to detect toxic oligomers in people," said Daggett.
