April 13, 2009
A protein made in the brain showed early promise in halting and reversing age-related brain damage in rats, mice and monkeys. While it's a long way from animals to humans, the findings open up a possible new avenue of research in the quest for effective Alzheimer's treatments.
The protein, called BDNF, for brain-derived neurotrophic factor, is normally made in the brains of mammals, including humans. Animals injected with the substance or implanted with a gene that produces BDNF showed less problems with thinking, learning and memory. Brain cells that should have died did not, and brain cells that had degenerated were revived in animals treated with the factor.
The study, by a research team at the University of California, San Diego, was published in the scientific journal Nature Medicine. The findings show early promise that BDNF treatment might potentially provide long-lasting protection by slowing, or even stopping, the progression of Alzheimer's disease.
"The effects of BDNF were potent," said Mark Tuszynski, M.D., Ph.D., professor of neurosciences at the U.C. San Diego School of Medicine. "When we administered BDNF to memory circuits in the brain, we directly stimulated their activity and prevented cell death from the underlying disease."
BDNF is normally produced throughout life in an area of the brain known as the entorhinal cortex that is important for memory. People with Alzheimer's make less of the substance.
Animals treated with BDNF performed better on a variety of learning and memory tasks. Notably, brain cells in the hippocampus, a portion of the brain critical for memory, were larger and showed stronger connections, signs that memory and other thought processes were being preserved. The hippocampus is one of the first areas of the brain damaged by Alzheimer's disease. If the animals continue in good health for the next year or so, trials might then be started in people, the researchers said.
"BDNF acts directly on dying cells in specific memory circuits of the brain," Dr. Tuszynski said. "In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment."
The protective and restorative effects of BDNF occurred independently of the build-up of beta-amyloid in mice genetically engineered to have a disease resembling Alzheimer's. Beta-amyloid is a protein that in its toxic form accumulates in the brain to form the plaques of Alzheimer's disease.
Many current experimental treatments for Alzheimer's disease target beta-amyloid production, so the potential role of BDNF as an alternative protective intervention is of great potential interest, Dr. Tuszynski said. Because BDNF targets a different set of disease mechanisms than amyloid modulation, there is also potential to combine BDNF and amyloid-based treatments, theoretically providing a two-pronged attack on the disease.
Alan H. Nagahara, David A. Merrill, Giovanni Coppola, et al: "Neuroprotective Effects of Brain-Derived Neurotrophic Factor in Rodent and Primate Models of Alzheimer's Disease." Nature Medicine, published online, February 8, 2009, doi:10.1038/nm.1912