A Northwestern University-led research team reports that insulin, by shielding memory-forming synapses from harm, may slow or prevent the damage and memory loss caused by toxic proteins in Alzheimer's disease.

The findings, which provide additional new evidence that Alzheimer's could be due to a novel third form of diabetes, was published Monday in the online edition of the Proceedings of the National Academy of Sciences.

In a study of neurons taken from the hippocampus, one of the brain's crucial memory centers, the scientists treated cells with insulin and the insulin-sensitizing drug rosiglitazone, which has been used to treat type 2 diabetes. (Isolated hippocampal cells are used by scientists to study memory chemistry; the cells are susceptible to damage caused by ADDLs, toxic proteins that build up in persons with Alzheimer's disease.)

The researchers discovered that damage to neurons exposed to ADDLs was blocked by insulin, which kept ADDLs from attaching to the cells. They also found that protection by low levels of insulin was enhanced by rosiglitazone.

ADDLs, short for "amyloid beta-derived diffusible ligands," are known to attack memory-forming synapses. After ADDL binding, synapses lose their capacity to respond to incoming information, resulting in memory loss.

The protective mechanism of insulin works through a series of steps by ultimately reducing the actual number of ADDL binding sites, which in turn results in a marked reduction of ADDL attachment to synapses, the researchers report.

"Therapeutics designed to increase insulin sensitivity in the brain could provide new avenues for treating Alzheimer's disease," said senior author William L. Klein, a researcher in Northwestern's Cognitive Neurology and Alzheimer's Disease Center. "Sensitivity to insulin can decline with aging, which presents a novel risk factor for Alzheimer's disease. Our results demonstrate that bolstering insulin signaling can protect neurons from harm."

(Xinhua News Agency February 3, 2009)