November 14, 2008
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Breakthrough in Alzheimer’s Research

In the November 14, 2008 issue of the journal Cell, researchers at the Fisher Center for Alzheimer’s Research at The Rockefeller University report a breakthrough in cellular analysis that solves a problem that has perplexed neurological research since the neuron was first discovered over 100 years ago.

Lead author, Myriam Heiman, and her colleagues have developed a method to reveal the kinds and amounts of proteins different cells produce, what biologists call its translational profile. The technique involves isolating the genetic messages that govern protein production in these different cell types. The new method, “translating ribosome affinity purification”, TRAP, can identify all the genetic messages that give that cell type its unique identity, including, perhaps, its susceptibility to disease.

Like skilled assassins, many diseases seem to know exactly what types of cells to attack. While destroying one type of cell, a disease will inexplicably spare a seemingly identical group of neighbors. What makes cells vulnerable or not depends largely on these translational profiles. For this reason, scientists have struggled to analyze the subtle molecular differences among the hundreds of specialized cell types that are tangled together in tissues like the brain.

The new TRAP procedure solves a problem that has been a fundamental barrier to a deeper understanding of the brain and how neurological diseases attack it. The true breakthrough lies in its ability to distinguish the profile of any cell type in any tissue in the body. Its usefulness is not just limited to brain cells, meaning it has far reaching research applications—cancer, heart disease, diabetes, as well as many others. Dr. Paul Greengard, the director of the Fisher Center for Alzheimer’s Research where Myriam Heiman is a Research Associate, says about half of the research in his lab now employs the new technique to study the biochemical bases of Alzheimer’s, Parkinson’s and other diseases. It is also being applied to the still-mysterious ways in which psychoactive drugs fight schizophrenia and depression.

The TRAP tool advances the speed at which researchers can yield results and should fundamentally change biochemical studies of the brain. “We can look at a thousand genes instead of one at a time, so things should clear a thousand times faster,” says Dr. Greengard, who won the Nobel Prize in Physiology or Medicine in 2000 for research into how neurons communicate.

This new technique will help accelerate scientific research into discovering the subtle molecular differences amongst the hundreds of specialized cell types. A deeper understanding of body cell mechanisms will help researchers investigate the causes of Alzheimer’s and Parkinson’s diseases.