Scientists supported by the BrightFocus 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, as published February 16 in BioMed Central's Molecular Neurodegeneration, the official journal of the BrightFocus 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). Therefore, Drs. Pritam Das, Todd Golde, and collaborators, were determined to show how the brain's immune response can counter the development of these plaques.
In this series of experiments, they delivered the immune protein Tumor Necrosis Factor alpha (TNFalpha) to the AD mice brains with 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, one of the corresponding authors of the study, located at the Mayo Clinic in Jacksonville, Florida. “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. These researchers plan to address these potential pitfalls in future studies.
On behalf of its donors, Alzheimer's Disease Research, a program of the BrightFocus Foundation, is proud to have funded Dr. Das for this very important work.
View the original journal article.