Stimulating Immune System In Mice That Have Been Designed To Mimic The Effects Of Alzheimer's Disease May Shrink Harmful Brain Plaques
CLARKSBURG, MD.-Scientists supported by the American Health Assistance Foundation have discovered that increasing the amount of an immune system protein in the brains of mice engineered to show features of Alzheimer's disease (AD) can reduce the amount of beta-amyloid in plaques. This study was published 16 February in BioMed Central's Molecular Neurodegeneration, the official journal of the American Health Assistance Foundation. This is the third immune protein that these researchers have linked to plaque reduction, providing ample rationale for developing new therapies.
Beta-amyloid is a short, “sticky” protein that collects in brain deposits called plaques, a hallmark of AD. These plaque deposits are associated with the death of surrounding brain cells, causing memory loss and other cognitive problems.
In addition to the direct effect of plaques, AD also is associated with inflammation or excessive action of the brain's immune cells (called microglia). Drs. Pritam Das, Todd Golde, and collaborators sought to determine how the brain's immune response can counter the development of these plaques.
In this series of experiments, the researchers delivered the immune protein Tumor Necrosis Factor alpha (TNFalpha) to the brains of these mice via a special viral delivery system. The resulting increase in TNFalpha expression seemed to reduce the amount of beta-amyloid protein deposits in the brain.
"In addition to IL-6 and INFgamma, we now show that TNFalpha also can significantly reduce amyloid deposition when expressed early in the disease process,” says Dr. Das of the Mayo Clinic in Jacksonville, Florida, one of the corresponding authors of the study. “These results support the notion that a future treatment for AD and other dementias could involve modulation of these initial inflammatory responses in the brain.”
One caveat to this study is that it's not known whether tipping the balance of the brain's natural defense mechanisms could translate into a safe human clinical treatment. The highly regulated immune system could be set off balance and may become toxic to surrounding cells. The researchers plan to address these potential pitfalls in future studies.
On behalf of its donors, Alzheimer's Disease Research-a program of the American Health Assistance Foundation-is proud to have funded Dr. Das for this important work.
Access to the original paper: “Hippocampal expression of murine TNFalpha results in attenuation of amyloid deposition in vivo” Paramita Chakrabarty , Amanda Herring , Carolina Ceballos-Diaz , Pritam Das and Todd E Golde. Molecular Neurodegeneration (2011), 6:16
About the American Health Assistance Foundation
The American Health Assistance Foundation (www.ahaf.org) is an international nonprofit organization dedicated to finding cures for age-related degenerative diseases. The foundation funds research on Alzheimer's disease, macular degeneration, and glaucoma and provides the public with free information about these diseases, including risk factors, preventative lifestyles, and current treatments and coping strategies.