Growing Cholinergic Nerve Circuits to Fight Alzheimer's

Most current medical treatments for Alzheimer's involves preserving brain cholinergic nerve function as long as possible. Nerve growth factors that improve brain cholinergic nerve growth might be very helpful for Alzheimer's Disease patients. Recent research has narrowed the search to the neurotrophins--and neurotrophin 3 in particular.

Richard Robertson, professor of anatomy and neurobiology, and other researchers from UCI's School of Medicine found that cholinergic nerve fibers grow toward sources of neurotrophin-3 during early development. In experiments with mice, without neurotrophin-3 to direct growth, the developing cholinergic nerve fibers appeared to not recognize their normal target cells in the brain. Because of this, the axon nerve fibers aided by these circuits grew irregularly and missed their specific target neural cells.

This finding, according to Robertson, has significant implications for neurodegenerative diseases like Alzheimer's. Cholinergic neuronal circuits play a key role in the proper information processing by the cerebral cortex and other areas of the brain. The cerebral cortex is the part of the brain that determines intelligence, personality, and planning and organization, and these actions are compromised by neurodegenerative diseases.

"Studies on the brains of Alzheimer's patients have shown a marked decline in these cholinergic circuits. Our work demonstrates that neurotrophin-3 is essential to maintain the connections to cerebral cortex neurons," Robertson said. "This study shows that a neurotrophin-3 therapy may be able to induce nerve fibers to regrow in the cerebral cortex, which would be beneficial to people with Alzheimer's."

In further studies on this subject, supported by a recently awarded three-year grant from the Alzheimer's Association, Robertson and his colleagues are testing the respective roles of nerve growth factor and neurotrophin-3 in a laboratory model of Alzheimer's disease. Laboratory rats with experimental damage to forebrain cholinergic circuits will be treated with either nerve growth factor or neurotrophin-3, or a combination of both, to determine their ability to produce anatomical, molecular and behavioral recovery.

Study results appear in the Dec. 1 issue of the journal Neuroscience.

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Tissue growth factors and their cell receptors are vital for ongoing tissue growth and repair, in both developing tissue and in mature tissue function and maintenance. While there is much more to Alzheimer's Disease than mere cholinergic brain function, there is little question that the preservation of cholinergic cortical circuits will help preserve much of the brain function lost in Alzheimer's Dementia.

Understanding the role of adult stem cells and brain derived tissue growth factors will change the outlook for dementia patients and patients with neurodegenerative diseases.