Body Science

Understanding dementia and Alzheimer’s Disease, through the latest developments in research.

Yale Researchers Reverse Alzheimer’s In Mice

Yale Researchers Reverse Alzheimer’s In Mice


Can you reverse the course of Alzheimer’s disease? Clinical studies say no. The mouse says you can.

Researchers at Yale School of Medicine may have made a big leap forward in Alzheimer’s research, according to Time and Newsweek. While it is important to note that mice studies are a far cry from human studies, the result is nonetheless promising and will shape the direction of future research.

It all starts with a protein called STEP, or STriatal-Enriched tyrosine Phosphate. STEP interferes with the ability of the human brain to learn and to create long-term memories by preventing synapses in the brain from strengthening. This then causes a myriad of potential conditions, including Alzheimer’s disease. (A higher level of STEP is also associated with Parkinson’s disease and schizophrenia.)

STEP was discovered by the lead author of the Yale study, Dr. Paul Lombroso, some 25 years ago. Today, we know that STEP attacks the glutamate receptors in the brain, which are responsible for turning our short-term memories into long-term memories.  Without this ability, one cannot recognize faces, memorize names, ride a bike or even learn spatial information such as how to navigate familiar areas.

Initially, levels of STEP in the mice were lowered genetically. This might not have been a treatment that was possible for humans, but it did let researchers know that they were definitely onto something. When STEP levels were lowered in mice who had been given the genes for Alzheimer’s, they performed the same cognitively as their healthy counterparts.

Dr. Lombroso found the results exciting, because they suggested that by inhibiting the activity of STEP, we might be able to reverse Alzheimer’s-related cognitive deficits.

Of course, researchers were faced with finding a means of lowering STEP that might one day be viable in humans.  Enter a compound known as TC-2153. This compound was given to the mice with Alzheimer’s disease. Amazingly, researchers saw a complete reversal of Alzheimer’s effects after only a single dose of the compound had been administered. The study made use of a variety of cognitive exercises that tested everything from recognition of previously seen objects to the ability to learn and remember different motor skills.

The Morris Water Maze is a great example of the types of tests that were performed. In this test, mice are placed in a basin of water with a platform located in one fixed section. There are symbols on the sides of the basin that the mice can use as markers to help them learn where the platform is.

A healthy mouse will quickly learn the location of the platform and swim to it, while this same task is impossible for a mouse with Alzheimer’s due to elevated levels of STEP. The mice given TC-2153, however, were able to memorize the location of the platform just as quickly as the healthy mice.

Dr. Lombroso was quick to point out to Newsweek that, while he is hopeful, there have been many drugs that have worked on mice but have not been successful in humans.

With that said, research is now being conducted to find more STEP inhibitors and to continue learning about the potential of TC-2153. Lombroso says that we must identify a “whole slew” of these inhibitors, as we never know which ones will pass the tests and make it onto the shelf at the pharmacy.

While a human drug using TC-2153 or another STEP inhibitor may still be a long way away, this study is one step closer for those hoping for a cure.


Gayle Day is a freelance writer based in Hinesburg, Vermont.

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