Five million Americans now have Alzheimer’s disease, and the number is only expected to grow as the population continues to age. There is no cure and no certain cause, and now even the prevailing theory on the origins of the disease is being called into question by new findings from Miller School scientists.

Previous research has shown that genetic defects in the mitochondrial energy production system in cells, specifically in the enzyme cytochrome c oxidase (COX), were found in the brains and other tissues of patients with the memory-robbing disease.

These findings led investigators to believe the gene defect caused an increase in cell-damaging free radicals within the mitochondria of Alzheimer’s patients. They theorized that these same free radicals damaged neurons and caused amyloid plaques to form in the brain, which are the hallmark of the disease.

Based on the prevailing theory, UM researchers studied a mouse model of Alzheimer’s disease in which there was an age-dependent accumulation of plaques and then knocked out the COX enzyme to see what would happen.

“Without the COX enzyme activity to protect them, we expected these animals would have many amyloid plaques, but we found just the opposite,” says Carlos T. Moraes, Ph.D., professor of neurology and cell biology and anatomy at the Miller School and lead author of the study. “Not only did these animals have fewer amyloid plaques than we expected, they also had less damage from free radicals. The findings suggest that the defect in the COX enzyme activity develops after the amyloid plaques and not before. This makes us think the defects in the COX activity are a consequence of the disease, not a cause.”

The findings published in the journal Proceedings of the National Academy of Sciences were obtained mostly by two members of Moraes’s research team: Hirokazu Fukui, M.S., a Lois Pope Fellow in the neuroscience graduate program, and Francisca Diaz, Ph.D., an assistant scientist in the Department of Neurology.

“Our findings clearly suggest free radicals may play an important role in developing Alzheimer’s disease, and they could be the target for possible new therapies,” says Moraes.