Researchers Identify Neuronal "Middleman" Involved in Development of Alzheimer's Disease

Finding points to possible new target for treatment

By Lois Baker

Release Date: December 16, 2004 This content is archived.


BUFFALO, N.Y. -- A potential new neuronal pathway involved in the development of Alzheimer's disease that may be a promising target for new treatments for the disease has been identified by scientists at the University at Buffalo.

The researchers have shown that the two known major features of Alzheimer's disease -- destruction of neurons that produce the neurotransmitter acetylcholine and the accumulation of beta-amyloid peptides, the major component of senile plaques found in the brains of Alzheimer's disease patients -- may be linked by a common pathway known as the GABAergic system.

A review of their research findings were published in the November issue of Current Alzheimer's Research.

Zhen Yan, Ph.D., and Jian Feng, Ph.D., associate and assistant professor, respectively, of physiology and biophysics in the UB School of Medicine and Biomedical Sciences, are the authors.

Acetylcholine has been recognized for some time as the critical element in cognition and memory.

"Most of the effective Alzheimer's disease drugs available currently are designed to preserve acetylcholine by deactivating the enzyme that degrades it," said Yan. "Our evidence indicates that the action of GABA, a neurotransmitter that puts the brakes on nerve impulses in the brain, preventing them from overreacting to a stimulus, plays an important role in working memory. It appears to control the timing of neuronal activities during cognitive operations.

"We found that acetylcholine, via the activation of its muscarinic type of receptors, may impact on cognition and memory functions by modifying neuronal excitability in the prefrontal cortex through this GABAergic system," she added. "In addition, we found that this critical function of acetylcholine is disrupted by beta-amyloid peptides and is enhanced by insulin. Consequently, drugs that enhance insulin actions or reduce beta-amyloid may facilitate the function of acetylcholine and improve cognition and memory," she said.

"This knowledge sheds light on the cellular and molecular basis of Alzheimer's disease and on how insufficient cholinergic function and beta-amyloid accumulation may be linked to cause cognitive impairments," said Yan. "It also opens the door to development of new pharmacological agents to treat this devastating disease."

The research is funded by the National Institute of Aging.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York.