Lead scientist Hani Atamna, Ph.D., found that alterations in the production of heme may be the key to understanding why excessive amyloid-beta is toxic to brain cells. Dr. Atamna had previously discovered that Alzheimer's patients have abnormal amounts of heme in their brains. In new research results, Atamna's team showed that amyloid-beta readily binds with heme to form a compound that can be flushed from cells. When there is insufficient heme or too much amyloid-beta, however, the amyloid-beta forms large toxic "clumps" that the cell cannot dissolve and eliminate.

Though heme binding with amyloid-beta can be beneficial, if too much heme is bound up with amyloid-beta, there may be insufficient heme available for the cell to function properly and the cell's mitochondria begin to decay. Dr. Atamna refers to this phenomenon as a "functional heme deficiency" because the cells are still forming heme, but it is trapped within an amyloid-beta/heme compound.

The researchers were surprised to discover that the heme/ amyloid-beta compound was a peroxidase – a type of enzyme that reacts harmfully with biological materials essential for proper brain function such as serotonin and L-DOPA. Dr. Atamna believes that the combination of functional heme deficiency, which harms mitochondria needed to produce energy, together with the increase in oxidative damage caused by the peroxidase, is what eventually kills the cell.

"Until now, we didn't understand all the factors that trigger Alzheimer's disease. The discovery of the formation of amyloid-beta peroxidase provides a clear picture of why cells die in the brain of Alzheimer's patients. Our next challenge is to develop drugs that directly and selectively target the excessive peroxidase of amyloid-beta, which could lead to the first significant therapy for Alzheimer's disease."

MEDICA.de; Source: Children's Hospital & Research Center at Oakland