By Sara Reeve

A USC team of scientists has published research that highlights a new potential therapeutic agent for patients with Alzheimer’s disease.

Researchers from the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC have found that a mutant protein helps to bind amyloid beta peptide in the brain more efficiently than a wild type — or naturally occurring — version. Amyloid beta peptide (Aβ) is a primary component of amyloid plaques — deposits found in the brains of Alzheimer’s disease patients — and most researchers believe it plays a central role in the development of Alzheimer’s.

In a study published May 24 in the Journal of Biological Chemistry, Berislav Zlokovic, director of the Zilkha Neurogenetic Institute, and colleagues demonstrate that the protein LRPIV-D3674G significantly improved Aβ clearance compared to the wild-type cluster IV. The clearing of Aβ in mice with Alzheimer’s disease-like symptoms has been shown to reduce those symptoms.

“The LRPIV mutant represents a new Aβ clearance therapy that we believe might work efficiently to prevent or remove accumulates of Alzheimer’s toxin Aβ from the brain,” said Zlokovic. “LRPIV works as a peripheral binding agent for Aβ and binds Aβ in the circulation without the need of crossing the blood-brain barrier. It creates a ‘sink’ for Aβ in the blood, which promotes Aβ efflux from brain to blood.”

The study, “A lipoprotein receptor cluster IV mutant preferentially binds amyloid-β and regulates its clearance from the mouse brain,” led by Abhay Sagare, assistant professor of research at the Keck School, showed that the mutant protein cleared Aβ in the mouse brain 25 to 27 percent better than the wild type version. After three months of treatment, mice treated with the mutant protein showed that Aβ levels in the hippocampus, cortex and cerebrospinal fluid were reduced by 60 to 80 percent, and cerebral blood flow responses and hippocampal function were improved.

According to Zlokovic, the research “presents us with a new therapeutic approach for Alzheimer’s disease based on prevention or removal of Aβ deposition in the brain. … It has a great therapeutic potential.”

Plans to develop LRPIV as a therapeutic agent for the treatment of Alzheimer’s disease are under way by ZZ Alztech, a Houston-based biotechnology company founded by Zlokovic and USC benefactor Selim Zilkha.

The research was supported by the National Institutes of Health (AG023084 and NS034467) and ZZ Alztech.