Low-Protein Slows Alzheimer’s

Mice with many of the pathologies of Alzheimer’s disease showed fewer signs of the condition when given a protein-restricted diet supplemented with specific amino acids every other week for four months.

At advanced stages of the disease, mice that were put on the new diet showed improved cognitive abilities over their nondieting peers when their memory was tested using mazes. In addition, fewer of their neurons contained abnormal levels of a damaged protein, called “tau,” which accumulates in the brains of Alzheimer’s patients.

Dietary protein is the major dietary regulator of a growth hormone known as IGF-1, which has been associated with aging and diseases in mice and several diseases in older adults.

Upcoming studies by Valter Longo, the study’s corresponding author and associate professor of neurobiology in USC Dornsife, will attempt to determine whether humans respond similarly — while simultaneously examining the effects of dietary restrictions on cancer, diabetes and cardiac disease.

“We had previously shown that humans deficient in growth hormone receptor and IGF-I displayed reduced incidence of cancer and diabetes,” said Longo, who directs the Longevity Institute of the USC Davis School of Gerontology. “Although the new study is in mice, it raises the possibility that low-protein intake and low IGF-I may also protect from age-dependent neurodegeneration.”

Longo worked with Pinchas Cohen, dean of USC Davis, as well as USC graduate students Edoardo Parrella, Tom Maxim, Lu Zhang, Junxiang Wan and Min Wei; Francesca Maialetti of the Istituto Superiore di Sanità in Rome; and Luigi Fontana of Washington University in St. Louis.

The results of the study were published online by Aging Cell in January.

The team found that a protein-restricted diet reduced levels of IGF-1 circulating through the body by 30 to 70 percent and caused an eightfold increase in a protein that blocks IGF-1’s effects by binding to it.

IGF-1 helps the body grow during youth but is also associated with several diseases later in life in both mice and humans. Exploring dietary solutions to those diseases as opposed to generating pharmaceuticals to manipulate IGF-1 directly allows Longo’s team to make strides that could help sufferers today or in the next few years.

“We always try to do things for people who have the problem now,” Longo said. “Developing a drug can take 15 years of trials and a billion dollars.

“Although only clinical trials can determine whether the protein-restricted diet is effective and safe in humans with cognitive impairment, a doctor could read this study today and, if his or her patient did not have any other viable options, could consider introducing the protein restriction cycles in the treatment — understanding that effective interventions in mice may not translate into effective human therapies,” he said.

Many elderly individuals may already be frail, lost weight or may not be healthy enough to eat a protein-restricted diet every other week.

Longo strongly insisted that any dieting be monitored by a doctor or registered dietician to make sure that patients do not become amino acid deficient, lose additional weight or develop other side effects.

This research was funded in part by National Institutes of Health grant P01AG034906.