JPost – untangling Alzheimer’s Disease

Researchers hope that eventually microRNA-325 can be used to create a drug to help Alzheimer’s patients maintain low levels of tomosyn and preserve brain function.
As the world’s population ages, the risk of developing Alzheimer’s disease rises, threatening to cause an even heavier burden on families and health systems for treating and caring for victims of this major cause of dementia.

Plaques and tangles made of proteins are believed to contribute to the debilitating progression of Alzheimer’s, but proteins also play a positive role in important brain functions such as cell-to-cell communication and immunological response. Molecules called microRNAs regulate both “good” and “bad” protein levels in the brain, binding to messenger RNAs to prevent them from developing into proteins.

Now, Dr. Boaz Barak and a team of researchers in the lab of Prof. Uri Ashery of Tel Aviv University’s neurobiology department have identified a specific set of microRNAs that harmfully regulate protein levels in the brains of mice with Alzheimer’s disease and beneficially regulate protein levels in the brains of other mice living in a stimulating environment.

“We were able to create two lists of microRNAs – those that contribute to brain performance and those that detract – depending on their levels in the brain,” said Barak.

“By targeting these molecules, we hope to move closer toward earlier detection and better treatment of Alzheimer’s disease.”

Prof. Daniel Michaelson of TAU’s Department of Neurobiology, Dr. Noam Shomron of TAU’s cell and developmental biology department, Dr. Eitan Okun of Bar-Ilan University and Dr. Mark Mattson of the US National Institute on Aging collaborated on the study, published recently in Translational Psychiatry.

Alzheimer’s disease is the most common form of dementia. Currently incurable, it increasingly impairs brain function over time, ultimately leading to death. The TAU researchers became interested in the disease while studying the brains of mice living in an “enriched environment” – an enlarged cage with running wheels, bedding and nesting material, a house, and frequently changing toys.

Such environments have been shown to improve and maintain brain function in animals much as intellectual activity and physical fitness do in people.

The researchers ran a series of tests on a part of the mice’s brains called the hippocampus, which plays a major role in memory and spatial navigation and is one of the earliest targets of Alzheimer’s in humans.

They found that, compared to mice in normal cages, the mice from the enriched environment developed higher levels of good proteins and lower levels of bad proteins. Then, for the first time, they identified the microRNAs responsible for regulating the expression of both good and bad proteins. Armed with this new information, the researchers analyzed changes in the levels of microRNAs in the hippocampi of young, middle-aged and old mice with an Alzheimer’s-like condition. They found that some of the microRNAs were expressed in exactly inverse amounts in mice with Alzheimer’s disease as they were in mice from the enriched environment.

The results were higher levels of bad proteins and lower levels of good proteins in the hippocampi of old mice with Alzheimer’s disease. The microRNAs the researchers identified had already been shown or predicted to regulate the expression of proteins in ways that contributed to the dementia.

Two findings appear to have particular potential for treating people with Alzheimer’s, the authors said. In the brains of old mice with the disease, microRNA- 325 was diminished, leading to higher levels of tomosyn, a protein that is well known to inhibit cellular communication in the brain. The researchers hope that eventually microRNA-325 can be used to create a drug to help Alzheimer’s patients maintain low levels of tomosyn and preserve brain function.

Additionally, the researchers found several important microRNAs at low levels starting in the brains of young mice. If the same can be found in humans, these microRNAs could be used as biomarker to detect Alzheimer’s at a much earlier age than is now possible – at 30 years of age, for example, instead of 60. “Our biggest hope is to be able to one day use microRNAs to detect Alzheimer’s in people at a young age and begin a tailor- made treatment based on our findings, right away,” concluded Barak.

MONEY FOR MARKS?

Paying your kids for getting good grades may not be the most effective way to motive them to do well in school, according to a Kansas State University study. Prof. Jared Durtschi, who teaches marriage and family therapy, said that while monetary compensation for grades may be effective in some cases, parents should also be aware that the practice could actually decrease their child’s motivation to perform well in school.

Paying children for good grades may cause their motivation to work hard in school to shift from an internal motivation – being motivated by how it will make them feel – to an external one that is driven by the reward they will receive.

“If a student’s motivation to apply himself or herself to academics is solely external, then the child will often stop working hard in school once he or she stops getting paid for their grades,” Durtschi said. “The practice has the potential to be especially harmful to pupils who are already internally motivated to get good grades. By paying these children for their achievements, parents risk making an activity they enjoy in its own right into something they feel they have to do in order to obtain some other end.”

In some cases, paying for good grades can be an effective method to motivate students who don’t feel driven to succeed on their own, Durtschi said. “Parents should work to transition the external motivation that comes with being paid to do something into an internal one, so that pupils will eventually become motivated to achieve in school on their own,” he said.

Many parents believe that motivating their children to get high grades pays off, because they are a significant factor in determining who will get into a top college or eventually secure a high-paying job. But Durtschi said money may not be the most meaningful reward to all. “The most powerful motivator is unique to each child,” he said. “For some kids, a trip to see grandma or not being required to do chores for a week might be more motivating than $20.”

He also believes that, especially for younger children, parental praise and affection often remain the most powerful motivator. In fact, he said, parents and teachers have the ability to significantly affect a child’s performance in the classroom merely by improving their perceptions of that child. “Even if a kid is just average, they can rise to so much more if expectations and treatment are adjusted. It limits our kids if we stop believing they are capable of great things.”