LOS ANGELES - The National Institute on Aging awarded UCLA Scientist David B. Teplow, Ph.D., professor of neurology at the David Geffen School of Medicine, a $7.9 million grant to study how brain proteins stick together abnormally to cause Alzheimer's disease. The multidisciplinary project will team up experts at Boston University, Massachusetts Institute of Technology and UCLA to assist Teplow in leading a national effort to uncover how the sticky proteins disrupt brain function.

In Alzheimer's disease, amyloid proteins clump together to form sticky plaques in the brain, interfering with cells' ability to communicate and eventually causing their death. This disruption results in the progressive memory loss and inability to think that typifies the disorder.

"Our consortium aims to illuminate — at the most fundamental cellular and biological levels — how the abnormal folding of proteins produces neurological disorders, and to translate our discoveries into effective treatments for Alzheimer's and other aging diseases," explained Teplow, principal investigator and director of the UCLA Biopolymer Laboratory.

Teplow's team suspects that structural changes to the amyloid proteins make them poisonous and lead to Alzheimer's. The researchers hope to unravel how the proteins form these toxins, and translate their findings into the design and testing of new drugs for Alzheimer's and other devastating neurological disorders caused by abnormal protein folding, including Huntington's, Parkinson's and prion diseases, such as Creutzfeldt-Jakob disease.

"We knew that no single approach could answer the question of how abnormal protein folding produces disease," he added. "A multidisciplinary program integrating the efforts of neurologists, physicists, chemists and biologists will create a synergy and potential for new therapies that five individual efforts could not."

According to Teplow, the study will be a minimum of five years and can be extended for substantially longer if continued progress is being made towards understanding Alzheimer's disease and other diseases of aging and towards development of therapeutic agents.

"We hope, by the end of the first five years of the grant, to have designed and synthesized novel therapeutic agents that can be tested in the laboratory in cell-free systems, in neurons grown in incubators, in laboratory animals, and finally in humans," Teplow said.

The multi-site team includes Gal Bitan, Ph.D., assistant professor of neurology at UCLA; George B. Benedek, Ph.D., the Alfred H. Caspary Professor of Physics and Biological Physics at MIT; Michael Bowers, Ph.D., professor of chemistry at UCSB; and H. Eugene Stanley, Ph.D., university professor at Boston University.

"It is our thesis that only through such broad, multidisciplinary efforts will cures for Alzheimer's disease and other disorders of aging be achieved," Teplow said. "The interdisciplinary strategy promises to advance efforts towards a cure at an accelerated rate. In addition, the superb clinical trials capabilities at UCLA will allow rapid translation of our basic science findings to the clinic."

Photo 1: Courtesy of Patrick Miller/UCLA Dept. of Neurology

David B. Teplow, Ph.D., professor of neurology at the David Geffen School of Medicine at UCLA

Photo 2: Courtesy of UCLA

UCLA Neurology Professor David Teplow with MIT Physics Professor George Benedek (left)