Versatile proteins could be new target for Alzheimer's drugs

A class of proteins that controls visual system development in the young brain also appears to affect vulnerability to Alzheimer's disease in the aging brain. The proteins, which are found in humans and mice, join a limited roster of molecules that scientists are studying in hopes of finding an effective drug to slow the disease process.

"People are just beginning to look at what these proteins do in the brain. While more research is needed, these proteins may be a brand new target for Alzheimer's drugs," said Carla Shatz, Ph.D., the study's lead investigator. Dr. Shatz is a professor of biology and neurobiology at Stanford University in California, and the director of Stanford's interdisciplinary biosciences program, BioX.

She and her colleagues report that LilrB2 (pronounced "leer-bee-2") in humans and PirB ("peer-bee") in mice can physically partner with beta-amyloid, a protein fragment that accumulates in the brain during Alzheimer's disease. This in turn triggers a harmful chain reaction in brain cells. In a mouse model of Alzheimer's, depleting PirB in the brain prevented the chain reaction and reduced memory loss.

The research was funded in part by the National Eye Institute, the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS), all part of the National Institutes of Health. It is reported in the Sept. 20 issue of Science.

"These findings provide valuable insight into Alzheimer's, a complex disorder involving the abnormal build-up of proteins, inflammation and a host of other cellular changes," said Neil Buckholtz, Ph.D., director of the neuroscience division at NIA. "Our understanding of the various proteins involved, and how these proteins interact with each other, may one day result in effective interventions that delay, treat or even prevent this dreaded disease."

Alzheimer's disease is the most common cause of dementia in older adults, and affects as many as 5 million Americans. Large clumps - or plaques - of beta-amyloid and other proteins accumulate in the brain during Alzheimer's, but many researchers believe the disease process starts long before the plaques appear. Even in the absence of plaques, beta-amyloid has been shown to cause damage to brain cells and the delicate connections between them.

Dr. Shatz's discovery took a unique path. She is a renowned neuroscientist, but Alzheimer's disease is not her focus area. For decades, she has studied plasticity - the brain's capacity to learn and adapt - focusing mostly on the visual system.

"Dr. Shatz has always been a leader in the field of plasticity, and now she's taken yet another innovative step - giving us new insights into the abnormal plasticity that occurs in Alzheimer's disease," said Michael Steinmetz, Ph.D., a program director at NEI. "These findings rest squarely on basic research into the development of the visual system." NEI has funded Dr. Shatz for more than 35 years.