DEC 07, 2016 7:59 AM PST

Scripps Florida Scientists Uncover Potential Driver of Age- and Alzheimer's-Related Memory Loss


JUPITER, FL – December 7, 2016 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have made an important discovery toward the development of drugs to treat age-related memory loss in diseases like Alzheimer’s. They found that reduced levels of a protein called Rheb result in spontaneous symptoms of memory loss in animal models and are linked to increased levels of another protein known to be elevated in the brains of Alzheimer’s disease patients.

Their study, led by TSRI Associate Professor Srinivasa Subramaniam, was published recently online ahead of print in the journal Neurobiology of Aging.
 

Link to Known Alzheimer’s Trigger


In the new study, Subramaniam’s group investigated the link between Rheb and an important enzyme called BACE1, which is elevated in older adults and people with Alzheimer’s disease.

“We know that Rheb regulates BACE1, which is a major drug target in Alzheimer’s disease,” Subramaniam said. “Studies of the autopsied brains of Alzheimer’s patients have found a significant reduction in Rheb, so it is possible that an increase in Rheb could reverse the buildup of amyloid plaque or help reduce or even reverse age-related memory loss.”

To uncover the impact of eliminating Rheb, Subramaniam and his colleagues put genetically altered mice through a battery of behavior tests beginning at around six months of age.

While Rheb depletion did not affect the overall body weight or motor activity of the animals, it did have subtle and selective effects on certain memory tasks they performed, such as navigating a maze and memory recall. The researchers compared these symptoms to memory deficits that occur in humans with Alzheimer’s disease and related dementia.

They also found that Rheb depletion increased BACE1 levels, which was consistent with previous research showing that higher BACE1 levels may be a contributing factor for memory deficits.

The fact that some research shows that Rheb messenger RNA is induced during protein starvation in fruit flies, led Subramaniam and his colleagues to theorize that a high-protein diet in humans might be a risk factor for decreasing Rheb levels with age, resulting in mild-to-severe cognitive deficits, as seen in animal models.

“This is an indication that nutrient signaling might regulate cognitive functions in mammals through alteration of Rheb–BACE1 pathway activity,” Subramaniam said.

“Overall, our study demonstrates that forebrain Rheb depletion promotes aging-associated cognitive defects,” said Neelam Shahani, the first author of the study. “Targeting the Rheb pathway may offer some therapeutic potential for aging- or Alzheimer’s disease-associated memory deficits.”

In addition to Subramaniam and Shahani, other authors of the study, “Forebrain Depletion of Rheb GTPase Elicits Spatial Memory Deficits in Mice,” are TSRI’s Wen-Chin Huang, Megan Varnum and Damon T. Page.

This work was supported by the National Institutes of Health (grants NIH/NINDS R01-NS087019, NIH/NINDS R01-NS094577, and NIH/NIMH R01-MH105610), Ms. Nancy Lurie Marks and the Alzheimer’s Disease Association (grant 2015-NIRG-344356).

This article was originally published on Scripps.edu.
About the Author
  • The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists-including two Nobel laureates-work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
You May Also Like
APR 24, 2020
Health & Medicine
APR 24, 2020
Study Shows Marijuana Withdrawal is Real
Whether or not an addiction to marijuana is a risk of the drug has been widely debated, with the general population typi ...
APR 27, 2020
Cardiology
APR 27, 2020
Almost Half of College Female Athletes Have High Blood Pressure
According to the World Health Organization (WHO) an estimated 1.13 billion people worldwide have hypertension, or high b ...
MAY 05, 2020
Microbiology
MAY 05, 2020
How a Microbe May Help Stop the Spread of Malaria
Scientists have discovered a bacterium that lives in mosquitoes around Lake Victoria, and appears to block malaria.
MAY 12, 2020
Immunology
MAY 12, 2020
Disabling Genes in Immune Cells Prevents Obesity
Obesity is a $1.7 trillion problem in the United States — a value almost 10% of the nation’s gross domestic ...
MAY 26, 2020
Genetics & Genomics
MAY 26, 2020
Some People May be Predisposed to Metastasis if They Get Cancer
Cancer can occur for many reasons and is influenced by many different factors, including genes and the environment. But ...
MAY 17, 2020
Technology
MAY 17, 2020
How Real is Video Game Addiction?
How real is video game addiction? We often hear of the negative implications for long-term video game use but is it fair ...
Loading Comments...