New Alzheimer's Drugs May Be Designed to Activate Peripheral Macrophages

Researchers seeking better treatment methods for Alzheimer's disease have found that in a mouse model stimulation of macrophages near the brain caused them to cross the blood-brain barrier and attack the amyloid plaques that characterize the disease.

Investigators at Cedars-Sinai Medical Center (Los Angeles, CA, USA) and Yale University (New Haven, CT, USA) genetically engineered mice in order to block the activity of transforming growth factor-f (TGF-f) an immunosuppressive molecule located on peripheral macrophages outside the brain. The investigators expected that the activated macrophages would cross into the brain and would increase the chronic level of inflammation caused by Alzheimer's. Instead, findings published in the May 30, 2008, online edition of the journal Nature Medicine revealed that the activated macrophages attacked amyloid plaques and reduced them in size by up to 90%. The genetically engineered mice showed improved brain performance, and macrophages isolated from these animals were found to be more effective at destroying plaque cells than macrophages from normal mice.

"Attempts to develop therapies for Alzheimer's disease have been difficult because most rely on getting a therapeutic molecule or antibody across the blood-brain barrier,” said first author Dr. Terrence Town, researcher in neurosurgery and biomedical sciences at Cedars-Sinai Medical Center. "The peripheral macrophages appeared to be attracted to the plaques, engulfing them, and by virtue of TGF-fÒ signaling blockade, they also appeared to be more voracious in eating the plaque than a wild-type (naturally existing) macrophage would be. If results from our study in mice engineered to develop Alzheimer's-like dementia are supported by studies in humans, we may be able to develop a drug that could be introduced into the bloodstream to cause peripheral immune cells to target the amyloid plaques.”


Related Links:
Cedars-Sinai Medical Center
Yale University