TAU discovery: Excess protein linked to Alzheimer's must be prevented before it accumulates on brain

TAU discovery Excess pr

elzheimer team fit doctor 248.88 (photo credit: Courtesy Michal Ben Ami)
elzheimer team fit doctor 248.88
(photo credit: Courtesy Michal Ben Ami)
Finding a treatment for Alzheimer's disease will be considerably more difficult than previously thought, now that a physiologist at Tel Aviv University's Sackler Faculty of Medicine has found that the formation of excess beta amyloid protein on the brain has to be prevented; simply removing it will not help. Once the protein is accumulated, Dr. Inna Slutsky found, it was too late to reverse the process and remove the beta amyloid, so the initiation process must be understood before effective drugs could be developed. Writing in the latest issue of the prestigious journal Nature Neuroscience, Slutsky reported that she and her team had discovered the cellular mechanism by which the protein functions in the brain. Although the connection between an excess of beta amyloid as tangles among the neurons and Alzheimer's has been known for some time, the team found that the protein has an important role in transmitting information among neurons in a healthy brain - thus a shortage of beta amyloid can be as dangerous as an excess is. Beta amyloid was found to regulate the transfer of electrical signals between the synapses (gaps between neurons) in the hippocampus, the brain region responsible for learning and memory. Slutsky, working with her students Efrat Abramov, Iftach Dolev, Hila Fogel and Eyal Ruff, in cooperation with Dr. Guiseppe Ciccotosto of the University of Melbourne, said beta amyloid is not - as previously thought - a toxic substance. "It is a neuroimmodulator," said Slutsky, who told The Jerusalem Post on Sunday that their just-published article is "our first paper since I opened my lab three years ago." She came on aliya from the former Soviet Union in 1990 and received all her university education at the Hebrew University, doing post-doctoral work at the Massachusetts Institute of Technology, she said. "We want to further understand the mechanism of what we have discovered," she continued. "Then we hope that could lead to the development of drugs that could prevent the formation of too much protein, rather than just destroy it." Alzheimer's disease is a brain disorder named for German physician Alois Alzheimer, who first described it in 1906. It is a fatal and progressive disease whose prevalence is growing significantly with the aging of the population and is among the top eight causes of death. The latest Israeli personality whose Alzheimer's disease was disclosed is Yaffa Yarkoni, the great songstress, who - according to her daughter - has had the dementia for the last eight years and is currently oblivious to the fact that she was a singer at all. The TAU team found that an increase in the concentration of the protein leads to a decline in the number of synapses and harm to the cellular process (called synaptic plasticity) responsible for learning and memory. They proved that beta amyloid has an important physiological role in transmitting information in neural networks. "To our surprise, we found that a significant decline in the concentration of the protein also harms the cellular function responsible for learning and memory. Thus there must be an optimal concentration of beta amyloid so that data can be transferred and processed properly, while too much or too little disrupts the process," said Slutsky. Most research on the influence of beta amyloid has been carried out until now on transgenetic mice in whose brains more of the protein is produced. But Slutsky said these posed problems: They did not make it possible to study the preliminary processes that cause Alzheimer's because the protein began appearing during the mice's early stages of development. In addition, they are relevant to only one type of dementia - that with a family history that begins at a relatively young age and is due to genetic mutations. But the genetic type is relevant only to one percent of all Alzheimer's cases. Sporadic cases that appear later may come from harm to the apparatus in which the protein breaks down, rather than is overproduced. So the team chose a different technique. Instead of raising mice with a high production of beta amyloid, they halted the production of an enzyme named neprilysin, which helps break down the protein.