Blood clots could be the "culprits" behind many of the symptoms of Alzheimer's disease; new research suggests a compound could stall the progression of the disease by interfering with the amyloid-β protein that plays a role in clot formation.
New experiments in Sidney Strickland's Laboratory of Neurobiology and Genetics at Rockefeller University has identified the compound that fights the plaque-forming protein. The work was published in the June 2 issue of The Journal of Experimental Medicine.
Many potential Alzheimer's drugs have attempted to target amyloid-β in the past, but have failed or cause serious side effects. This new drug interferes with the protein's ability to bind to a clotting agent in the blood.
"Our experiments in test tubes and in mouse models of Alzheimer's showed the compound, known as RU-505, helped restore normal clotting and cerebral blood flow. But the big pay-off came with behavioral tests in which the Alzheimer's mice treated with RU-505 exhibited better memories than their untreated counterparts," Strickland said. "These results suggest we have found a new strategy with which to treat Alzheimer's disease."
The researchers pinpointed RU-505 out of a pool of 93,716 candidates selected from compound libraries. The team aimed to find a compound that interfered with the interaction between fibrinogen and amyloid-β.
"We tested RU-505 in mouse models of Alzheimer's disease that over-express amyloid- β and have a relatively early onset of disease. Because Alzheimer's disease is a long-term, progressive disease, these treatments lasted for three months," Hyung Jin Ahn, a research associate in the lab, said. "Afterward, we found evidence of improvement both at the cellular and the behavioral levels."
The mice that were treated had less inflammation in the brain and the blood to their brains was closer to a normal flow than in the untreated mice.
"While the behavior and the brains of the Alzheimer's mice did not fully recover, the three-month treatment with RU-505 prevents much of the decline associated with the disease," Strickland said.
