Alzheimer’s Disease Preventative Strategy Works in Mice

A compound known as fisetin inhibits progressive memory and learning deficits associated with Alzheimer’s disease in mice. Fisetin is found in many fruits and vegetables and, if consumed daily, prevents progressive memory loss.

Fisetin, a compound found in many fruits and vegetables, has been shown to inhibit memory loss associated with Alzheimer's disease in mice.

Fisetin, a compound found in many fruits and vegetables, has been shown to inhibit memory loss associated with Alzheimer’s disease in mice.

December 17, 2013 –Pamela Maher and her team at Salk Institute for Biological Studies developed a groundbreaking preventative strategy in mice for one of the top ten causes of death in the United States, Alzheimer’s disease.

Mice with mutations in two genes connected with Alzheimer’s disease were tested. Some were provided with daily dosages of fisetin, found in various fruits and vegetables. Other mice were given no dosages of the compound. Over a course of nine months, researchers tested the memory and learning abilities of mice using water mazes.

At the nine-month mark, the mice without the daily dosage of fisetin began performing poorly in the water mazes. Conversely, mice receiving fisetin performed as well as normal mice at both nine months and a year old.

Maher’s stated, “even as the disease would have been progressing, the fisetin was able to continue preventing symptoms.”

Maher’s team collaborated with scientists at the University of California, San Diego for the next step. The brains of mice that had and had not received the fisetin dosage were tested to examine the levels of different molecules.

Traditionally, Alzheimer’s disease has been associated with the accumulation of amyloid B-plaques and tau tangles, which lead to neuron dysfunction and death. However, recently it has become clear that Alzheimer’s disease involves disruptions in a variety of cellular systems. For example, the team determined that in all mice that exhibited symptoms of Alzheimer’s disease, the pathways that dictated cellular inflammation were turned on. However, the mice that were provided daily dosages of fisetin showed less active cellular inflammation pathways and contained anti-inflammatory molecules within their brain.

Additionally, Maher’s team found that fisetin reduces the levels of p25 in the brain. P25, which causes prolonged activation of cyclin-dependent kinases 5 (Cdk5), has been shown to accumulate in patients with Alzheimer’s disease. Ultimately, elevated levels of p25 lead to neuroinflammation and neurodegeneration that are commonly associated with Alzheimer’s disease.

Both discoveries point to the possibility that fisetin may provide a new approach to Alzheimer’s disease treatment. Maher’s team would like to continue researching the surprising effect that fisetin has on mice prone to Alzheimer’s disease.

Maher recognizes that her team has developed a preventative model while human patients do not seek a doctor until they are struck with memory problems. As a result, Maher would like to test whether fisetin is not only capable of preventing memory loss, but also if it has the ability to stop memory loss from progressing once symptoms are present.

Maher’s study is a step forward to finding a way to prevent and treat Alzheimer’s disease. The fact that fisetin inhibits progressive memory loss as well as prevents certain cellular inflammation pathways points to a new approach to treatment.

 

Kayleigh Makoid

Dickinson College

 

Antonio Currais, Marguerite Prior, Richard Dargusch, Aaron Armando, Jennifer Ehren, David Schubert, Oswald Quehenberger, Pamela Maher.  (17 December 2012). Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice. Aging Cell, 1: 3-47

 

About Kayleigh Makoid