Blocking Brain Protein Could Stop Aging Memory Loss

It is no secret that as people get older things are harder to remember. This happens because as people age, their brain chemistry changes. The body contains a protein that interrupts the brain’s cell repair system, as people age, this protein, beta2-microglobin (B2M), builds up in the cerebrospinal fluid and the blood. This buildup of protein has been proven to alter how mice are able to perform in memory tests. Scientists are conducting a study to determine if removing the protein could save the aging memory.

Researchers are well on their way to finding medications that will minimize the buildup of B2M. They will soon be able to test humans to determine if the protein affects memory and use the medication as a possible solution. Saul Villeda, a researcher from the University of California in San Francisco is responsible for the original discovery of detailed research of an “anti-elixir” factor, the protein responsible for brain degeneration.

Much of the research that is focused on age reversal is looking into “elixir” factors, which are simply agents that bring back youth. As an example, when the blood from a young mouse is injected into an old mouse, brain and muscle degeneration is stopped, broken bones heal, and heart damage is prevented. At this point, scientists believe that the best way to tackle the aging process is through treatments that combine pro-youthful factors with medications that are able to neutralize pro-aging agents such as B2M.

The human body produces the protein in order to assist the immune system in being able to know the difference between human cells and foreign cells. It also has a part in developing the nervous system. However, as people age, the protein builds up preventing the brain from creating new cells. At this point, it is unknown what causes the protein to build-up.


Villeda’s research team injected B2M into the blood or brain of young mice. After the injection, the young mice did as poorly as the elderly mice in two different types of memory tests. After the B2M naturally eliminated itself from the younger mice, which took 30 days, their performance returned to normal. This may mean that it is possible to reverse the effects of B2M.

Villeda had genetically engineered mice that did not produce this protein and they performed the same at any age. Benjamin Alman from the Hospital for Sick Children in Toronto, Canada, does not believe B2M is the only factor that causes memory loss as people age. Alman is currently researching the molecules in the young blood that make bones heal faster. He does state that the possibility of memory loss being halted by medications, which would interfere with the circulating factors was unthinkable not that long ago and he is excited to see this research move forward.

Elevated levels of B2M have been found in patients with cognitive disorders associated with aging and even those with Alzheimer’s. First, Villeda’s team measured the protein in the blood of mice and people of varying ages and confirmed that the levels are increased with age. Then researchers injected the protein into three-month-old mice and discovered that these mice were having issues with memory loss. They struggled to complete a water maze, the mice made more than twice the mistakes after they had been trained to get through the maze. This occurred because these mice had less new neurons than other young mice. Villeda believes that this ongoing research proves that the blood can be manipulated instead of the brain in an effort to treat memory impairment. This is a much easier endeavor when thinking of human patients. This could mean that removing the protein B2M would save cognitive memory loss.


This current study gives a solid confirmation of previous studies showing that the protein had a significant role in memory loss with age, according to Irina Conboy, a biologist with the University of California, Berkeley. Conboy published a paper stating that targeting a different molecule can decrease these protein levels and restore the creation of new brain cells. Conboy says that the truth lies in clinical trials that will prevent the production of B2M. It will only be known for sure then if blocking the protein would be a worthwhile treatment to prevent memory disorders.

A series of studies have been conducted and are ongoing that are looking into molecules in the blood that are or may be associated with aging. Tony Wyss-Coray is a researcher from Stanford University, and while working with other researchers, it has been confirmed from these and other studies mentioned, that injecting older mice with the blood of younger mice seems to reverse age-related cognitive function and vice-versa.

Villeda is a former postdoc in the Wyss-Coray lab. As a professor, Villeda had a desire to study blood factors that are implicated in previous studies that contribute to aging, such as B2M in the hopes of reversing the memory loss or saving thoughts of years past by removing the protein. It has been well-known by scientists that B2M has a role in pruning nerve cell connections in young, developing brains.

By Jeanette Smith
Edited By Leigh Haugh

New Scientist–Blocking Brain Protein Could Stop Memory Loss Caused by Aging
Science Magazine–‘Old-age Protein’ May Cause Memory Loss
C&EN–Blood Protein Linked to Age-Related Memory Loss

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Second Photo Courtesy of Laura Dahl’s Flickr Page – Creative Commons License
Third Photo Courtesy of ZEISS Microscopy of Flickr Page – Creative Commons License

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